Hereditary macular dystrophies

BACKGROUND: Orthostatic hypotension is a common phenomenon in the elderly. Hormonal changes during orthostatic stress have been described in elderly normotensive people and in those with essential hypertension. However, the hormonal response in elderly people who have systolic hypertension during orthostasis has not yet been quantified. METHODS: In this study we investigated 14 non-diabetic men, aged 60 to 75 years, with untreated systolic hypertension who were subjected to 45 degrees passive head-up incline on a tilt table for 15 min. Their hormonal profile and hemodynamic changes were analyzed before and after the stress. RESULTS: In the supine position, plasma levels of norepinephrine, atrial natriuretic peptide and aldosterone were in the normal range, while the plasma renin activity was low. Immediately upon tilt the systolic blood pressure fell but it reverted to baseline values after 15 min of orthostasis. At that time the cardiac output decreased while the systemic vascular resistance and the plasma norepinephrine concentration rose. The atrial natriuretic peptide appeared to fall, and the renin-aldosterone level did not change. CONCLUSION: The physiologic response to orthostatic stress in elderly people with systolic hypertension is comparable to that of elderly normotensive people and those with essential hypertension, i.e. a decrease in cardiac output and an increase in plasma norepinephrine levels. The atrial natriuretic peptide appeared to fall appropriately. The response of the renin-aldosterone system mimicked that in elderly patients with low renin essential isolated hypertension. These observations may have a bearing on the management of elderly people with systolic hypertension who also have orthostatic symptoms; they may not require a different approach from that needed for others of the same age group.     

Effects of head-down tilt on atrial natriuretic peptide and the renin system in pregnancy

We studied the effects of head-down tilt to 10 degrees for 30 minutes on plasma atrial natriuretic peptide and the renin-aldosterone system in 8 preeclamptic pregnant women, 8 healthy pregnant women, and 11 nonpregnant women of fertile age. Mean arterial blood pressure did not change in the pregnant groups but increased significantly in the nonpregnant control subjects. Heart rate decreased significantly in preeclamptic women but remained unchanged in both control groups. Baseline atrial natriuretic peptide concentration was significantly higher in both preeclamptic (66 +/- 4 pmol/L) and pregnant (54 +/- 6 pmol/L) control subjects compared with nonpregnant subjects (40 +/- 2 pmol/L), but the difference between the pregnant groups was not significant. Head-down tilting induced a significant increase in atrial natriuretic peptide only in healthy pregnant women. Baseline plasma renin activity and aldosterone concentrations were significantly higher in pregnant control subjects compared with both the preeclamptic and nonpregnant groups. The differences between the preeclamptic and nonpregnant control groups were nonsignificant. After head-down tilting, plasma renin activity decreased significantly only in nonpregnant control subjects, whereas aldosterone decreased significantly in preeclamptic and nonpregnant control subjects. In preeclampsia, atrial natriuretic peptide release followed blood pressure and not changes in cardiac output. When all 27 women were studied, a correlation between atrial natriuretic peptide and mean arterial pressure was found in the left lateral supine position. The results suggest that pregnant women developing preeclampsia lose their usual hemodynamic control and show reactions resembling the nonpregnant state when subjected to head-down tilt.     

Effects of sodium chloride and relative humidity on growth and sporulation of moulds isolated from cured fish

1. The aim of this study was to determine plasma levels of N-terminal atrial natriuretic peptide and atrial natriuretic peptide in normal subjects and in patients with essential hypertension, cardiac transplant and chronic renal failure, using radioimmunoassays directed towards the mid-portion pro-atrial natriuretic peptide (31-67) and pro-atrial natriuretic peptide (1-30) of the N-terminal atrial natriuretic peptide and atrial natriuretic peptide (99-126). The circulating form(s) of the immunoreactive N-terminal atrial natriuretic peptide in plasma extracts has been investigated using all three radioimmunoassays by means of gel filtration chromatography to further clarify the major immunoreactive molecular circulating form(s) of N-terminal atrial natriuretic peptide in man. 2. The plasma level (mean +/- SEM) of N-terminal pro-atrial natriuretic peptide (31-67) in the normal subjects was 547.2 +/- 32.7 pg/ml (n = 36) and was significantly elevated in patients with essential hypertension (730.2 +/- 72.3 pg/ml, P < 0.025, n = 39), in cardiac transplant recipients (3214.0 +/- 432.2 pg/ml, P < 0.001, n = 9) and in patients with chronic renal failure (3571.8 +/- 474.1 pg/ml, P < 0.001, n = 11). Plasma levels of N-terminal pro-atrial natriuretic peptide (1-30) and atrial natriuretic peptide were similarly elevated in the same patient groups when compared with the mean plasma values in the normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial natriuretic peptide metabolism during pregnancy in the rat

OBJECTIVE: Our purpose was to determine whether plasma clearance rates and production rates of atrial natriuretic peptide 99-126 are altered during pregnancy in the rat. STUDY DESIGN: Twelve virgin and 12 late-pregnant chronically instrumented, conscious, unrestrained Sprague-Dawley rats were studied. Mean arterial pressure, heart rate, and plasma atrial natriuretic peptide levels were measured before and during a 40-minute continuous infusion of atrial natriuretic peptide (10 ng/kg/min). RESULTS: Control mean arterial pressure was 106 +/- 5 mm Hg in virgin rats versus 97 +/- 4 mm Hg in pregnant rats. Atrial natriuretic peptide infusion did not significantly affect mean arterial pressure in either group of animals but decreased heart rate in virgin rats. Basal plasma atrial natriuretic peptide levels were significantly higher in virgin than in pregnant rats (107 +/- 10 vs 78 +/- 7 pg/ml, respectively, p < 0.05). Atrial natriuretic peptide infusion significantly increased plasma levels in both groups to similar (183 +/- 19 and 154 +/- 14 pg/ml, virgin vs pregnant rats). Calculated plasma clearance rates were similar in virgin and pregnant rats (166 +/- 27 vs 155 +/- 17 ml/kg/min). Estimated production rates of atrial natriuretic peptide were higher in virgin then in pregnant rats (15.1 +/- 1.4 vs 11.4 +/- 1.1 ng/kg/min, p < 0.05). CONCLUSIONS: Plasma atrial natriuretic peptide levels are lower in chronically instrumented near-term pregnant rats compared with levels in virgin rats. This is not related to differences in plasma atrial natriuretic peptide clearance rates but rather to a decrease in production rates in late pregnancy.     

Serum endothelin and atrial natriuretic peptide in cirrhotic patients with ascites and hepatorenal syndrome

BACKGROUND: The pathogenesis of cirrhotic ascites and hepatorenal syndrome remains unresolved. The involvement of both endothelin-1 and atrial natriuretic peptide have recently been suggested. This study investigated the concentrations of serum endothelin and atrial natriuretic peptide in cirrhotic patients. METHODS: Seven healthy subjects and 31 cirrhotic patients were studied. Cirrhotic patients were divided into three groups: Group I, 16 cirrhotic patients without ascites; Group II, 10 cirrhotic patients with ascites, but without hepatorenal syndrome; and Group III, five cirrhotic patients with hepatorenal syndrome and ascites. Their sera were analyzed for endothelin-1 and atrial natriuretic peptide concentrations. RESULTS: Cirrhotic patients with ascites, Group II and Group III, had higher plasma endothelin-1 concentrations (15.9 +/- 2.3 pg/ml and 24 +/- 2.1 pg/ml, respectively) than normal subjects and compensated cirrhotics (3.8 +/- 0.7 pg/ml and 6.4 +/- 1.1 pg/ml, respectively); p < 0.001). Atrial natriuretic peptide concentrations were also significantly higher in cirrhotic patients than in normal subjects (p < 0.025). Plasma endothelin-1 concentration had a negative correlation with creatinine clearance (r = -0.65, p < 0.001), as did atrial natriuretic peptide concentrations (r = -0.44, p = 0.012). Plasma endothelin-1 correlated significantly with atrial natriuretic peptide concentrations (r = 0.38, p = 0.035). CONCLUSIONS: Both endothelin-1 and atrial natriuretic peptide concentrations were elevated in cirrhotic patients with ascites and hepatorenal syndrome. Endothelin-1 may have a negative impact on renal function. Our data also suggested that impaired responsiveness rather than impaired secretion of atrial natriuretic peptide is responsible for sodium retention in cirrhotic patients with ascites.     

Acute and chronic neutral endopeptidase inhibition in rats with aortocaval shunt

In heart failure, sodium and water retention develop despite elevated plasma levels of atrial natriuretic peptide. Atrial natriuretic peptide is degraded in part by a neutral endopeptidase. Whether neutral endopeptidase inhibition improves sodium and water excretion in heart failure is unknown. We determined the effect of neutral endopeptidase inhibition on plasma levels of atrial natriuretic peptide and the renal response to acute volume expansion in rats with aortocaval shunts and in sham-operated controls. Acute endopeptidase inhibition with SQ 28,603 (30 mg/kg) elevated atrial natriuretic peptide plasma levels in both shunted rats (523 +/- 54 to 1258 +/- 330 pmol/L, P<.05) and controls (184 +/- 28 to 514 +/- 107 pmol/L, P<.05). Urinary cGMP excretion, which reflects renal action, increased in parallel. However, the diuretic and natriuretic responses to acute volume expansion were enhanced only in control rats and not in shunted rats. In contrast to the acute effects, chronic neutral endopeptidase inhibition with SCH 34826 (30 mg/kg twice daily) in shunted rats did not change atrial natriuretic peptide plasma levels or cGMP excretion. Nevertheless, the diuretic and natriuretic responses to acute volume load were increased by chronic endopeptidase inhibition in shunted rats (1789 +/- 154 to 2674 +/- 577 microL/80 min and 99 +/- 31 to 352 +/- 96 micromol/80 min, respectively; P<.05). Chronic endopeptidase inhibition attenuated the cardiac hypertrophic response to aortocaval shunt without changing arterial blood pressure. Our data show that the renal effects of neutral endopeptidase inhibition are not necessarily dependent on changes in atrial natriuretic peptide plasma levels but instead may be mediated by local inhibition of the neutral endopeptidase in the kidney. In addition, chronic endopeptidase inhibition may attenuate heart failure-induced cardiac hypertrophy independent of hemodynamic effects.     

Effect of the Cox maze procedure on the secretion of atrial natriuretic peptide

OBJECTIVES: The Cox maze procedure has been confirmed to be effective in curing atrial fibrillation. Some authors have reported severe fluid retention after the Cox maze procedure and have suggested decreased secretion of atrial natriuretic peptide as a possible mechanism. This study was designed (1) to examine the serial changes in atrial natriuretic peptide after the Cox maze procedure as compared with changes occurring after coronary artery bypass grafting and (2) to elucidate any differences in atrial natriuretic peptide levels between patients with transient recurrence of atrial fibrillation after the Cox maze procedure and those without recurrence of atrial fibrillation. METHODS: Blood samples were drawn from the right and left atria in patients undergoing the Cox maze procedure (n = 19) and from the right atrium in patients undergoing coronary artery bypass grafting (n = 6) before and 1, 2, and 3 days after the operation. In six patients undergoing the Cox maze procedure, samples were also drawn from the radial artery before and 1, 2, 3, 5, and 7 days after the operation. The plasma samples were prepared by refrigerated centrifugation and stored until radioimmunoassay. In the Cox maze procedure group, atrial natriuretic peptide levels in the right atrium were 629 +/- 366, 154 +/- 112, 162 +/- 112, and 183 +/- 97 pg/ml and those in the left atrium were 276 +/- 168, 152 +/- 91, 162 +/- 111, and 145 +/- 80 pg/ml before and 1, 2, and 3 days after the operation, respectively. A marked decrease in atrial natriuretic peptide levels was evident after the Cox maze procedure (p < 0.001). There was no significant correlation between atrial natriuretic peptide levels and atrial pressures after the Cox maze procedure, which suggests that secretion of atrial natriuretic peptide by the atria was impaired. There was a significant correlation between the atrial natriuretic peptide levels in the left atrium and those in the peripheral radial artery, and the decreased levels of atrial natriuretic peptide in the radial artery continued for 7 days after the Cox maze procedure. There were no differences in the atrial natriuretic peptide levels between the patients with transient recurrence of atrial fibrillation (n = 6) and those without recurrence (n = 13) after the Cox maze procedure. In the coronary artery bypass grafting group, the atrial natriuretic peptide levels in the right atrium were 115 +/- 37, 124 +/- 48, 154 +/- 54, and 156 +/- 36 pg/ml before and 1, 2, and 3 days after the operation, respectively. No change was seen after the operation. CONCLUSIONS: We observed a significant decrease in atrial natriuretic peptide levels after the Cox maze procedure. This may be one of the possible causes of fluid retention after this procedure. These decreased atrial natriuretic peptide levels after the Cox maze procedure may result from the multiple atriotomy incisions and excision of both atrial auricles performed during the procedure, rather than from the conversion of atrial fibrillation to normal sinus rhythm.     

Awareness and attitudes concerning BRCA gene testing

We studied the changes in pulmonary hemodynamics induced by arm-stretching exercise in 12 patients with chronic pulmonary emphysema (CPE) and 9 control subjects (Controls). Both patients and control subjects underwent right heart catheterization with inspired gas analysis at rest and during exercise for the 6 minute-exercise test. Mean pulmonary arterial pressure (mPAP) in patients with CPE significantly increased from 18.5 +/- 3.9 mmHg at rest to 25.7 +/- 5.1 mmHg during exercise without decreased oxygen tension of the arterial blood. Both mPAP and total pulmonary resistance increased in proportion to the increases in cardiac output. Mixed venous plasma atrial natriuretic peptide (ANP) was significantly evaluated during exercise in patients with CPE, but did not in Controls. There were a significantly positive relationships between ANP and mPAP, and a significantly negative relationships between ANP and PvO2 during exercise. These results suggest that pulmonary hypertension during light exercise in cases of CPE may be caused by deterioration of the pulmonary capillary bed, and that ANP may be a useful indicator for evaluating pulmonary hypertension in patients with CPE.     

Prognostic value of plasma catecholamines, plasma renin activity, and plasma atrial natriuretic peptide at rest and during exercise in congestive heart failure: comparison with clinical evaluation, ejection fraction, and exercise capacity

Survival in congestive heart failure is related to plasma catecholamines and atrial natriuretic peptide at rest, but the prognostic importance of changes during exercise is unknown. The aim of this study was to evaluate the prognostic value of catecholamines and atrial natriuretic peptide at rest and during maximal exercise in congestive heart failure, and to compare it to clinical and exercise test variables and left ventricular ejection fraction. One hundred ninety consecutive patients (136 men and 54 women; median age, 66 years; range, 42-75 years) with clinically stable congestive heart failure were included. Sixteen patients were in New York Heart Association class I, 87 in class II, 83 in class III, and 4 in class IV. Left ventricular ejection fraction was 0.30 (range, 0.06-0.74). Total survival after 1 year was 79%, after 2 years, it was 68%. Prognostic variables at univariate analysis were: plasma noradrenaline at rest (P < .0001), plasma adrenaline at rest (P = .049), and atrial natriuretic peptide at rest (P = .016). During exercise, plasma catecholamines and plasma atrial natriuretic peptide increased significantly; the change, however, was not related to survival. Six variables carried significant, independent prognostic information in a multivariate analysis: left ventricular ejection fraction (P = .03), plasma noradrenaline at rest (P = .009), New York Heart Association class III + IV (P = .005), increase in heart rate during exercise < or = 35 min-1 (P < .0001), serum creatinine > 121 mumol/L (P = .004), and serum urea > 7.6 mmol/L (P = .007). Patients with congestive heart failure have a poor survival despite intensive medical treatment. Plasma catecholamines and plasma atrial natriuretic peptide are elevated at rest and rises further during exercise; the increase, however, is not related to mortality. Plasma noradrenaline at rest contributes with further prognostic information despite knowledge of clinical and exercise variables and was the only neurohormonal variable with independent, significant prognostic information on survival.     

Personality, smoking and inflammatory bowel disease

OBJECTIVE: To quantify the hemodynamic effects of turning critically ill, mechanically ventilated patients to the extreme left and right lateral postures. DESIGN: Prospective investigation. SETTING: Eight-bed intensive care unit in a university hospital. PATIENTS: Twelve consecutive patients presenting with severe respiratory failure and requiring continuous positive inotropic support. INTERVENTIONS: All patients were mechanically ventilated and placed in a kinetic treatment system. They were positioned in the supine, left dependent, and right dependent postures, resting for 15 min in each position. MEASUREMENTS AND RESULTS: Hemodynamic measurements, assessments of right ventricular function, and determinations of intrathoracic blood volume were performed in three different positions. Concentrations of atrial natriuretic peptide in plasma were quantified. In three patients, the findings were controlled by transesophageal echocardiography. Cardiac index [median (range) 5.5 (3.2-8.1) vs 4.3 (3.2-7.5) l/min per m2, p < 0.01], intrathoracic blood volume [1125 (820-1394) vs 1037 (821-1267) ml/m2, p < 0.01], and right ventricular end-diastolic volume [130 (83-159) vs 114 (79-155) ml/m2, p < 0.05] increased significantly in the left dependent position compared to supine. Mean arterial pressure did not change. Atrial natriuretic peptide levels rose from 140 to 203 pg/ml. In the right dependent position, we found a marked decrease in the mean arterial pressure [85 mmHg (supine) to 72 mmHg (right dependent), p < 0.01]. Cardiac index and intrathoracic blood volume were unchanged, but right ventricular end-diastolic volume decreased from 114 to 102 ml/m2 (p < 0.05). Additionally, atrial natriuretic peptide levels decreased significantly (median delta value: 37 pg/ml). In echocardiographic controls we found an increase in right ventricular end-diastolic diameters in the left dependent position and shortened diameters in the right dependent position. CONCLUSIONS: Extreme lateral posture affects the cardiovascular system in critically ill, mechanically ventilated patients: in the left dependent position a "hyperdynamic state" is reinforced, while the right decubitus position impairs right ventricular preload and predisposes to hypotension. Echocardiography and changes in plasma atrial natriuretic peptide values indicate that these findings are due to altered distensibility of the right ventricle caused by regional intrathoracic gravitational changes. We conclude that the duration and the angle of lateral posture should be restricted in hemodynamically unstable patients.     

Plasma levels of natriuretic peptides and adrenomedullin in elderly hypertensive patients: relationships to 24 h blood pressure

OBJECTIVE: The aim of this study was to investigate the relationships between levels of natriuretic peptides and adrenomedullin and 24 h blood pressure levels in elderly hypertensives. DESIGN AND METHODS: We performed both 24 h ambulatory blood pressure monitoring and measurement of plasma levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and adrenomedullin in 118 asymptomatic hypertensive elderly (> 60 years old) patients. We classified the subjects into groups with isolated clinic hypertension (n = 40) and sustained hypertension (n = 78). We also measured the levels of these peptides in 37 elderly normotensive subjects. RESULTS: Plasma ANP and BNP levels were slightly increased in patients with isolated clinic hypertension compared with elderly normotensives. Among the hypertensives, plasma ANP and BNP levels were more closely related to 24 h blood pressure levels than to office blood pressure levels. Sustained hypertensives showed significantly increased plasma levels of ANP and BNP compared with isolated clinic hypertensives, while adrenomedullin levels were similar in the two groups. Elderly hypertensives with left ventricular hypertrophy detected by electrocardiography had significantly higher levels of ANP and BNP, and higher BNP/ANP ratios than those without left ventricular hypertrophy, while there was no significant difference in adrenomedullin levels between the two groups. CONCLUSIONS: Our results suggest that measurements of ANP and BNP may be useful in detecting left ventricular hypertrophy and in differentiating isolated clinic hypertension from sustained hypertension in elderly hypertensive patients.     

Magnetic resonance imaging in the early diagnosis of cavernous sinus thrombosis

The pathophysiology of preeclampsia has not been fully clarified. A variety of factors have been implicated with this disease including vasoactive peptides and hormones during the last 20 years. Inadequate generation of atrial natriuretic peptide (ANP) has been one of the mechanisms discussed as to possibly contribute to the development of hypertension. In human pregnancy multiple studies of ANP-plasma-concentration in normal or hypertensive pregnancies showed conflicting results. The complexity of the clinical findings of hypertension in pregnancy makes it very difficult to carry out comparative clinical and biochemical studies in humans. In an animal experience genetic as environmental influences could be excluded. Therefore, the present study shows an experimental preeclampsia-like syndrome in the rat by reduction of the utero-placental flow. We observed a significant increase of plasma ANP in pregnant rats with experimentally induced hypertension. Furthermore, our results suggest that the ventricles could be an important source of ANP gene expression.     

Nocturnal blood pressure and relation to vasoactive hormones and renal function in hypertension and chronic renal failure

The purpose of this study was to assess the blood pressure profile and to measure vasoactive hormones in patients with essential hypertension (n=61), secondary hypertension (n=32) and chronic renal failure (n=32) matched with healthy control subjects (n=35), and to study the relationship between circadian changes in blood pressure and baseline levels of vasoactive hormones and renal function. Non-invasive, automatic blood pressure measurement was performed for 24 or 48 h. Venous plasma concentrations of renin, angiotensin II, aldosterone, arginine vasopressin, atrial natriuretic peptide and endothelin were measured. The mean 24-h blood pressure was higher in all groups of hypertensive patients than in control subjects. The nocturnal blood pressure fall was preserved in essential hypertension, in contrast to secondary hypertension in which it was attenuated. In the patients with chronic renal failure the 24-h mean blood pressure was the same as in the controls. Night-time blood pressure was higher among the chronic renal failure patients than in the control group, and the nightly blood pressure fall in both diastolic and systolic blood pressure was reduced. Plasma concentrations of renin activity, arginine vasopressin, atrial natriuretic peptide, aldosterone and endothelin were significantly increased in secondary hypertension and chronic renal failure, compared to essential hypertension and control subjects. Plasma angiotensin II was increased in chronic renal failure compared to essential hypertension and controls. Estimated creatinine clearance and nightly blood pressure dips were inversely correlated in essential and secondary hypertension, i.e. with a decreasing renal function both systolic and diastolic nightly blood pressure dips were gradually attenuated. In the whole group of patients the nightly systolic and diastolic blood pressure dips were negatively correlated to basal plasma renin activity, plasma aldosterone and atrial natriuretic peptide levels, i.e. the higher the basal plasma hormone level the lower the blood pressure dip. In conclusion, patients with essential hypertension have elevated but normally configured 24-h blood pressure profiles, and patients with different kinds of secondary hypertension have elevated 24-h blood pressure profiles and attenuated nightly systolic and diastolic blood pressure falls. The more the renal function is reduced and the more the plasma levels of renin and aldosterone are increased, the more the nocturnal fall in blood pressure is reduced. It is suggested that the attenuated or absent decrease in nocturnal blood pressure in secondary renal hypertension is caused by an abnormally increased secretion of vasoactive hormones and/or by so far unknown factors released from the diseased kidney.     

Perindopril postmarketing surveillance: a 12 month study in 47,351 hypertensive patients

We investigated the effect of electrical cardioversion of atrial fibrillation in patients with heart failure. The study group consisted of 24 patients with mild to moderate heart failure [13 men, mean age 67+/-7 years, mean peak oxygen consumption (peak VO2) 16.3+/-2.8 ml/min/kg] and chronic atrial fibrillation (median duration 19 (1-228) months). Patients were stable on digoxin, diuretics, nitrates and angiotensin converting enzyme inhibitors; no prophylaxis with antiarrhythmics was started after cardioversion. Cardioversion was unsuccessful in 6 patients; of the 18 patients in whom sinus rhythm was obtained 9 had a relapse of atrial fibrillation within 6 weeks after cardioversion. The remaining 9 patients with maintenance of sinus rhythm and the 15 (6+9) patients with atrial fibrillation at follow-up after 6 weeks did not differ with respect to any baseline characteristic, including age, peak VO2, duration of atrial fibrillation, echocardiographic left ventricular and left atrial dimensions, plasma atrial natriuretic peptide and norepinephrine. In the patients with maintenance of sinus rhythm, baseline measurements were repeated at follow-up. Peak VO2 did not change significantly (16.7+/-2.8 to 17.6+/-3.3 ml/min/kg, P=0.29); also, echo parameters, atrial natriuretic peptide and norepinephrine were not significantly affected. These results indicate that it is difficult to achieve lasting sinus rhythm through electrical cardioversion in patients with atrial fibrillation and mild to moderate heart failure. Moreover, in patients with maintenance of sinus rhythm after cardioversion no significant benefit in terms of peak VO2, cardiac dimensions, and neurohumoral status is to be expected. Hence, indiscriminate cardioversion of atrial fibrillation in the setting of heart failure does not appear to be useful.     

Concentration of neuropeptide Y in serum of patients with primary hypertension

Neuropeptide Y (NPY) has been recently characterized as a circulating vasoconstrictor peptide which is co-stored with noradrenaline in sympathetic neurons. To investigate the role of NPY concentration in hypertension we measured the circulating NPY, endothelin-1,2 (ET-1,2), atrial natriuretic peptide (ANP), aldosterone, plasma renin activity (PRA) and noradrenaline (NA) in patients with stable mild to moderate primary hypertension. Circulating levels of NPY, ET-1,2, ANP, aldosterone and PRA were measured with radioimmunoassay, NA by double-isotope radioenzymatic assay. There were significant increase in concentrations NPY, ET-1,2, ANP and NA in patients with moderate primary hypertension, and significant positive correlations between the plasma levels of NPY, ET-1,2 and NA.     

The effects of atrial natriuretic peptide infusion on hemodynamic, renal, and hormonal responses during gastrectomy

Atrial natriuretic peptide (ANP) antagonizes the reninangiotensin-aldosterone, adrenocorticotropic hormone-cortisol, vasopressin, and endothelin systems. Surgical injury stimulates these systems and causes vasoconstriction and antidiuresis. We assessed the hemodynamic, renal, and endocrine effects of continuous intravenous infusion of ANP in patients anesthetized with sevoflurane undergoing gastrectomy. ANP (0.1 microgram.kg-1.min-1; ANP group, n = 9) or saline (control group, n = 9) was infused continuously for 3 h from the start of the operation. The ANP group showed much higher urinary volume and sodium, potassium, and chloride excretion than the control group, although the former had lower arterial blood pressure. ANP infusion slightly inhibited aldosterone secretion and initially tended to inhibit renin secretion stimulated by surgery, but it did not affect surgery-induced increases in the plasma concentrations of vasopressin, adrenocorticotropic hormone, cortisol, or endothelin. Two patients in the ANP group experienced excessive hypotension, one experienced bradycardia, and two experienced mild hypoxemia, which required treatment but were resolved easily. These findings suggest that ANP infusion may be used with caution for controlling renal function and arterial blood pressure during surgery. Implications: Continuous intravenous infusion of atrial natriuretic peptide, 0.1 microgram.kg-1.min-1, during gastrectomy was associated with higher water and sodium excretion and lower arterial blood pressure. It tended to inhibit the renin-angiotensin-aldosterone system compared with saline infusion, which suggests that atrial natriuretic peptide may be useful for intraoperative circulation control.     

Augmentation of the cardiac natriuretic peptides by beta-receptor antagonism: evidence from a population-based study

OBJECTIVES: The present retrospective analysis of data derived from a population-based study examined the relationship between intake of beta-receptor antagonists and plasma concentrations of the cardiac natriuretic peptides and their second messenger. BACKGROUND: Beta-receptor antagonists are widely used for treatment of cardiovascular disease. In addition to direct effects on heart rate and cardiac contractility, recent evidence suggests that beta-receptor antagonists may also modulate the cross talk between the sympathetic nervous system and the cardiac natriuretic peptide system. METHODS: Plasma concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and their second messenger cyclic guanosine monophosphate (cGMP) were assessed in addition to anthropometric, hemodynamic and echocardiographic parameters in a population-based sample (n = 672), of which 80 subjects used beta-receptor antagonists. RESULTS: Compared to subjects without medication, subjects receiving beta-receptor antagonists were characterized by substantially elevated ANP, BNP and cGMP plasma concentrations (plus 32%, 89% and 18%, respectively, p < 0.01 each). Analysis of subgroups revealed that this effect was highly consistent and present even in the absence of hypertension, left atrial enlargement, left ventricular hypertrophy or left ventricular dysfunction. The most prominent increase was observed in a subgroup with increased left ventricular mass index. By multivariate analysis, a statistically significant and independent association between beta-receptor antagonism and ANP, BNP and cGMP concentrations was confirmed. Such an association could not be demonstrated for other antihypertensive agents such as angiotensin-converting enzyme inhibitors or diuretics. CONCLUSIONS: Beta-receptor antagonists appear to augment plasma ANP, BNP and cGMP concentrations. The current observation suggests an important contribution of the cardiac natriuretic peptide system to the therapeutic mechanism of beta-receptor antagonists.     

Increased brain natriuretic peptide and atrial natriuretic peptide plasma concentrations in dialysis-dependent chronic renal failure and in patients with elevated left ventricular filling pressure

Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations were measured in patients with dialysis-dependent chronic renal failure and in patients with coronary artery disease exhibiting normal or elevated left ventricular end-diastolic pressure (LVEDP) (n = 30 each). Blood samples were obtained from the arterial line of the arteriovenous shunt before, 2 h after the beginning of, and at the end of hemodialysis in patients with chronic renal failure. In patients with coronary artery disease arterial blood samples were collected during cardiac catheterization. BNP and ANP concentrations were determined by radioimmunoassay after Sep Pak C18 extraction. BNP and ANP concentrations decreased significantly (P < 0.001) during hemodialysis (BNP: 192.1 +/- 24.9, 178.6 +/- 23.0, 167.2 +/- 21.8 pg/ml; ANP: 240.2 +/- 28.7, 166.7 +/- 21.3, 133.0 +/- 15.5 pg/ml). The decrease in BNP plasma concentrations, however, was less marked than that in ANP plasma levels (BNP 13.5 +/- 1.8%, ANP 40.2 +/- 3.5%; P < 0.001). Plasma BNP and ANP concentrations were 10.7 +/- 1.0 and 60.3 +/- 4.0 pg/ml in patients with normal LVEDP and 31.7 +/- 3.6 and 118.3 +/- 9.4 pg/ml in patients with elevated LVEDP. These data demonstrate that BNP and ANP levels are strongly elevated in patients with dialysis-dependent chronic renal failure compared to patients with normal LVEDP (BNP 15.6-fold, ANP 2.2-fold, after hemodialysis; P < 0.001) or elevated LVEDP (BNP 6.1-fold, ANP 2.0-fold, before hemodialysis; P < 0.001), and that the elevation in BNP concentrations was more pronounced than that in ANP plasma concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Arterial hypertension in patients on chronic hemodialysis

Arterial hypertension is frequent among chronically dialyzed patients. The kidney obviously plays a major role in arterial blood pressure control. There is a large number of experimental data emphasizing different factors (in addition to renin important in renal hypertension prognosis) such as: sodium balance, angiotensin, etc [1-8]. Sympathetic activity disorders or lack of vasodilatory prostaglandins and quinine may also play a certain role. In uremic patients peripheral arteriolar resistance is increased, unlike normotensive uremic patients or those who prove to be normotensive upon clinical examinations [8, 11-15]. Hypertension occurs in approximately 80% of patients with chronic renal failure, producing a number of complications primarily affecting the CNS and systemic circulation [5-8, 10, 11, 13]. The study concerned patients on chronic dialysis, with a male to female ratio of 69.9%:32.1%. In most of them the underlying disease, which caused chronic renal failure, was glomerulonephritis (60.0%), then pyelonephritis (17.0%) and nephrosclerosis, nephrolithiasis, polycystic kidney and, finally, renal tumours. The effect of permanent haemodialysis during the first year of treatment, was efficacious on hypertension in 1704 (65.1%) patients; in 672 (25.7%) patients therapeutical effects were achieved by dialysis and antihypertensive drugs, while in 240 (9.2%) subjects there was no improvement. General observations suggest that two types of arterial hypertension persisted in patients with chronic renal failure: volume-dependent arterial hypertension which is more frequent (90-95%) among haemodialyzed patients and renin-dependent hypertension. Such findings are of utmost importance indicating that hypervolaemia is one of the major factors in the development of arterial hypertension in patients with chronic renal failure, with renin playing the secondary role. Salt-free diet should be used in the treatment of arterial hypertension for years, a well conducted haemodialysis is highly effective in the control of arterial hypertension among these patients. In our series of patients dialysed three times a week; normalization of blood pressure was faster with lower incidence of hypertensive crises during haemodialysis and with few complications. Water and sodium excess was reduced by frequent haemodialyses and sudden changes in electrolyte, hydrostatic and other metabolic effects were minimized. Increased values of plasma renin activity were observed in a small number of patients. Ultrafiltration is insufficient for normalization of blood pressure. Hypertensive crises were frequent in these patients. Their response to medicaments such as methyldopa, beta-adrenergic blockers or other antihypertensive drugs, was good. Severe changes in blood vessels, especially in fundus oculi blood vessels were frequent in these patients. The life of hypertensive glomerulonephritis patients was especially endangered (graphs 1-6). In addition to the mentioned factors arterial hypertension during haemodialysis may also be of cardiac origin, including increase in cardiac output due to arteriovenous anastomosis, disequilibrium syndrome, changes in osmotic gradient of both extra- and intracellular spaces with resultant arteriolar wall oedema, erythrocyte amount, hypoxia, composition of dialysis fluid (sodium concentration), plasma osmotic pressure, metabolic acidosis and other factors. More recently, natriuretic hormone has also been indentified as a cause of vascular refraction. Peripherial arteriolar resistance as a cause of arterial hypertension among uremic patients must not be forgotten, because the genesis of arterial hypertension in patients with chronic renal failure is multifactorial. The highest percentage refers to volume-dependent arterial hypertension, whereas the percentage of other aetiologic factors is lower. Haemodialysis enables the normalization of blood pressure in most of hypertensive patients.     

Different secretion patterns of adrenomedullin, brain natriuretic peptide, and atrial natriuretic peptide during exercise in hypertensive and normotensive subjects

The purpose of this study was to investigate the effect of exercise on plasma concentrations of adrenomedullin, brain natriuretic peptide (BNP), and atrial natriuretic peptide (ANP) in patients with essential hypertension (n = 15) and in normotensive controls (n = 10). Exercise consisted of two fixed workloads, 40 and 80 watts of work load using a supine bicycle ergometer. Plasma levels of all three peptides at rest were significantly higher in hypertensives than in controls. Plasma concentrations of ANP increased with exercise in both groups and had greater increments in hypertensive patients than in normotensives. Plasma concentrations of BNP increased only in patients with hypertension and the levels of increase correlated with basal plasma BNP levels (r = 0.94, p < 0.001) and with left ventricular mass (r = 0.62, p < 0.01) determined by echocardiography. In contrast, plasma adrenomedullin did not change with exercise in either group. These results suggest that secretion patterns of these peptides are regulated by different mechanisms and that the amount and kind of peptides mobilized by exercise may depend on the underlying diseases or pathophysiologic condition.