A study on the pathogenesis of hyporeninemia in diabetics

Hyporeninemic hypoaldosteronism has mainly been described in patients with diabetes mellitus. In order to elucidate the mechanisms of hyporeninemia in diabetic patients, the author studied the response of active renin concentration (ARC) and inactive renin concentration (IRC) to the administration of captopril or sodium depletion in patients with diabetes mellitus and glomerulonephritis and in normal subjects. The diabetic patients were separated into four groups: Group 0, diabetic patients without neuropathy or nephropathy; Group I, those with neuropathy without nephropathy; Group II, those without neuropathy with nephropathy; Group III, those with neuropathy and nephropathy. Diabetic patients with some complications had slightly lower plasma active renin levels than those without complications. The mean increase in plasma active renin after captopril (delta ARC) and sodium depletion was lower in group I than in group 0, and there was no difference between group II and group 0. There was no correlation between delta ARC and creatinine clearance (Ccr) in diabetes mellitus. Plasma prorenin was higher in group I than in group 0, and there was no difference between group II and group 0. No significant change of prorenin after captopril was observed in all groups, but the mean increase in plasma inactive renin after sodium depletion was slightly higher in groups I and III than in groups 0 and II. ARC/IRC was significantly lower in group I than in group 0, and there was no difference between group II and group 0. There was no correlation between ARC/IRC and Ccr in diabetes mellitus, but significant correlation between ARC/IRC and postural change in systolic blood pressure. In three diabetic patients with hyporeninemic hypoaldosteronism, the postural fall in systolic blood pressure was significant, and ARC/IRC was significantly low, but IRC was not high. These results suggest that autonomic dysfunction is a major factor in an impairment of the processing of prorenin to active renin in diabetic patients, and severe autonomic dysfunction may impair the biosynthesis of prorenin in patients with hyporeninemic hypoaldosteronism.     

Renin response and angiotensinogen control during graded hemorrhage and shock in the dog

Hemorrhage and hemorrhagic hypotension have been shown to be potent stimulators of renin release. However, the relationship between angiotensinogen consumption and angiotensinogen production has yet to be completely defined during this type of circulatory stress. Peripheral renin activity increased progressively as the blood pressure was decreased stepwise by hemorrhage to 50 mmHg and remained elevated throughout the shock phase of the experiment. Angiotensinogen did not change from control (809 ng/ml) throughout hemorrhabic hypotension and shock. During hemorrhagic hypotension, with the infusion of the angiotensin antagonist, [1-sarcosine, 8-alanine]angiotensin II, angiotensinogen concentration fell progressively from 693 to 208 ng/ml at 50 mmHg. Intravenous angiotensin II infused continuously after the mean blood pressure reached 50 mmHg significantly elevated plasma angiotensinogen concentration. In conclusion, during hemorrhagic hypotension and shock, the kidney and the liver appeared capable of maintaining elevated plasma renin activity and adequate plasma renin substrate, angiotensinogen, respectively. The mechanism responsible for the maintenance of plasma angiotensinogen is suggested to involve a positive-feedback effect of angiotensin II on the liver.     

The effect of pindolol on plasma renin activity and blood pressure in hypertensive patients

1 The effect of pindolol administered to twenty-six patients with hypertension of unknown origin was compared with respect to blood pressure and plasma renin activity change after increase of the dose over a period of 6 weeks. 2 There was no clear correlation between the fall of plasma renin activity, which in some patients was very marked, and the fall in blood pressure. Some patients with a fall in plasma renin activity did not drop their pressure. Conversely, some with a fall of pressure did not drop their plasma renin activity. 3 The addition of hydrochlorothiazide to the pindolol finally caused further lowering of the blood pressure in all but one patient and the plasma renin activity rose in all but two patinets. There was no clear correlation between change in plasma renin activity and the effect on blood pressure.     

Prevalence, predisposing factors, and prognostic importance of postural hypotension

OBJECTIVES: To determine the prevalence and predisposing factors of postural hypotension and to evaluate the effect of postural hypotension on 10-year vascular mortality in an elderly population. METHODS: A random sample of 480 subjects aged 65 years or older was obtained in 1982. The participation rate of the subjects in the study was 72%, for a total of 347 subjects. Orthostatic testing and continuous ambulatory electrocardiographic recording, as well as comprehensive clinical evaluation, including medical history, physical examination, standard electrocardiography, chest radiography, blood pressure measurement, routine biochemical analysis, and determination of body mass index, were performed. In 1992, the 10-year mortality of subjects and causes of death were recorded from the mortality statistics. Of the participants, 184 (53%) had died and 163 were still alive. To determine the effect of postural hypotension on the 10-year mortality, the subjects who were alive and those who had died of vascular or nonvascular causes were compared. All of the examinations had been completed in 156 subjects who were still alive, in 109 subjects who had since died of vascular causes, and in 64 subjects who had died of nonvascular causes. RESULTS: An abnormal postural systolic blood pressure drop (-20 mm Hg or less) after standing for 3 minutes was demonstrated in 28.0% of subjects. There were no sex or age differences between the subjects with and without postural hypotension. No predisposing factors for postural hypotension other than elevated blood pressure were found. Chronic cardiovascular diseases, disability, body mass index, medication, and abnormal findings in ambulatory electrocardiographic monitoring were not associated with postural hypotension. In the univariate analysis, the extent of systolic or mean blood pressure change predicted neither vascular nor nonvascular death during the 10-year follow-up. On the other hand, diastolic blood pressure drop, in particular after standing for 1 minute, was associated with increased vascular mortality (odds ratio, 2.7; 95% confidence interval, 1.3 to 5.6). In the multivariate analysis, however, this association disappeared. CONCLUSIONS: Postural hypotension was common in an unselected elderly population. No predisposing factors for postural hypotension other than elevated blood pressure were found. The 10-year follow-up showed that postural diastolic, but not systolic, blood pressure drop predicted excess vascular mortality. However, this association disappeared in the multivariate analysis, thus being related to background factors such as cardiovascular diseases.     

Postural dysregulation in systolic blood pressure is associated with worsened scoring on neurobehavioral function tests and leukoaraiosis in the older elderly living in a community

BACKGROUND AND PURPOSE: Postural hypotension, which occurs frequently in community-living, apparently healthy elderly adults, is usually asymptomatic. However, the relation between postural changes in blood pressure and quantitative higher cerebral function or silent brain lesions remains unclear. We examined the association of exaggerated postural changes in systolic blood pressure with cognitive and quantitative neurobehavioral functions and with brain lesions on MRI in the community-dwelling older elderly. METHODS: The study population consisted of 334 community-dwelling elderly adults, aged 75 years or older (mean age, 80 years). Postural changes in systolic blood pressure (SBP) were assessed using an autosphygmomanometer (BP-203 I). By the difference between the mean of two measurements of SBP at standing and at supine position (dSBP = SBP at upright-SBP at supine position), we divided the subjects into three groups: (1) 20 subjects with postural hypotension (d-SBP < or = -20 mm Hg), (2) 29 subjects with postural hypertension (dSBP > or = 20 mm Hg), and (3) 285 subjects with postural normotension (20 < dSBP < 20 mm Hg). We defined the former two groups as the postural dysregulation group. Scores in four neurobehavioral function tests (Mini-Mental State Exam. Hasegawa Dementia Scale Revised, computer-assisted visuospatial cognitive performance score, and the Up and Go Test) and activities of daily living were compared among the three groups. Brain lesions on MRI, including number of lacunes and periventricular hyperintense lesions, were compared among 15 age- and sex-matched control subjects with postural hypotension, 15 with postural hypertension, and 30 with postural normotension. RESULTS: Twenty subjects (6.0%) exhibited postural hypotension and 29 (8.7%) postural hypertension. Scores in neurobehavioral functions and activities of daily living were significantly lower in the postural dysregulation group (both postural hypotension and hypertension groups) than in the postural normotension group. The postural dysregulation group exhibited significantly more advanced periventricular hyperintensities than the normotension group. CONCLUSIONS: Asymptomatic community dwelling elderly individuals with postural hypotension as well as those with postural hypertension had poorer scores on neurobehavioral function tests and more advanced leukoaraiosis demonstrated on MRI than those without exaggerated postural changes in SBP.     

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.     

Effect of chronically infused adrenomedullin in two-kidney, one-clip hypertensive rats

The hypotensive effect of chronically infused adrenomedullin, a potent vasodilator peptide, was examined in conscious two-kidney, one-clip (2K-1C) hypertensive and sham-operated rats. They were infused with 1.0 microgram/h of synthetic human adrenomedullin for 14 days by means of osmotic minipumps. Control groups were infused on the same schedule with 0.9% saline. Systolic blood pressure was measured before and during the infusion. Plasma renin activity, aldosterone and human adrenomedullin concentrations were determined at day 14 of the infusion. A significant reduction of systolic blood pressure was observed in the adrenomedullin-infused 2K-1C rats at day 4, and systolic blood pressure remained significantly lower throughout the experiment compared to that of the control 2K-1C. A similar hypotensive effect was seen in the adrenomedullin-infused sham-operated rats. Both the plasma renin activity and aldosterone concentrations of the adrenomedullin-infused 2K-1C and sham groups were significantly reduced compared to those of the respective control, whereas, the plasma human adrenomedullin concentration in the adrenomedullin-infused groups was found to be within the physiological range. These findings demonstrated that chronically infused adrenomedullin had a hypotensive effect accompanied by significant reductions of plasma renin activity and plasma aldosterone concentration in 2K-1C hypertensive and sham-operated rats.     

Postural changes in plasma renin activity and responses to vasoactive drugs in a case of Shy-Drager syndrome

A male aged 47 years with gross autonomic insufficiency as part of the Shy-Drager syndrome is described. He did not sweat normally when warmed, and his circulatory responses to mental arithmetic, the Valsalva manoeuvre, and head-up tilt were abnormal indicating severe sympathetic failure. During head-up tilt there was a rise in plasma renin activity and plasma aldosterone. It is argued that plasma renin activity is not dependent on sympathetic nervous activity and may be mediated by renal baroreceptors. These rises may help sustain the blood pressure in such patients during repeated head-up tilts. Infusions of L-noradrenaline and angiotension produced greater hypertension, and injections of isoprenaline greater hypotension than in controls. Although it is difficult to exclude the possibility that one factor in this may be hypersensitivity of receptors in blood vessel walls, the principal factor is likely to be the absence of those baroreflexes of which the efferent pathways are in the sympathetic nervous system.     

Novel protein toxin-based strategy for development of cytotoxic T lymphocyte vaccines

Unexplained episodic hypertension, hypotension, or orthostatic intolerance, tachycardia, anxiety, and flushing in 21 patients were investigated for the possibility of hypovolemia by blood volume and individual plasma catecholamines (including autocrine paracrine-born dopamine), determinations baseline, in response to upright posture and catecholamines only during the episodic blood pressure swings. Blood volume was determined by Cr51 fixed to patients' hemoglobin, free norepinephrine, epinephrine, and dopamine with dopamine sulfate following sulfatase hydrolysis, radioenzymatically. The recumbent mean 27.4+/-3% (SE) blood volume decrease from predicted values accentuating to 33.5+/-4% upright was associated with normal baseline plasma free norepinephrine, epinephrine, dopamine, dopamine sulfate, plasma renin activity, and aldosterone with normal mean postural responses from all patients except a hyperresponsive compared to controls (p < 0.04), plasma renin activity increase from 0.657+/-0.1 to 4.47+/-1.8 ng/mL/hr. During the hypertensive, hypotensive, or tachycardic episodes the moderate increase of free norepinephrine and epinephrine (p < 0.04) (but not free dopamine) contrasted with an increase of dopamine sulfate from 2.5+/-0.9 to clearly pathological values of 16.8+/-8.3 ng/mL (p < 0.0003 on % increase of individual values). We conclude that the normal (but to the degree of hypovolemia inappropriately low orthostatism- and episodes-associated sympathetic arousal) is outpaced by considerable episodic dopamine sulfate surges, reflecting extraneuronal dopamine discharge. Whether this increase contributes to the increased natriuresis directly or by inhibiting aldosterone response to renin-angiotensin, perpetuating hypovolemia, remains to be established.     

Participation of renal, but not of submaxillary renin in the homeostasis of the blood pressure after experimentally induced hypotension in mice

While hypotension elicited a marked increase in plasma renin concentration in conscious normal mice, no increase was provoked in previously nephrectomized mice in spite of the high renin content of their submaxillary glands. The role of the increased release of renal renin for the homeostasis of the blood pressure was shown by the decrease in pressure which followed blockade of the renin system. Contrary to Saralasin which did not change the blood pressure in nephrectomized mice, injections of SQ 20.881 did in some mice result in a decrease in blood pressure, which was probably caused by its ability to inhibit bradykininases. Both Saralasin and SQ 20.881 elicited marked increases in plasma renin in normal, but not in nephrectomized mice, showing that, while renal renin release is controlled by the plasma angiotensin II concentration, this does not apply to submaxillary renin release.     

Medical and social factors affecting early teenage pregnancy. A literature review and summary of the findings of the Louisiana Infant Mortality Study

The acute effects of small doses of intravenous propranolol on renin release and on circulatory dynamics were studied at the time of renal arteriography in 12 persons with essential hypertension. All of the subjects had a normal peripheral renin response to chronic sodium depletion and all had normal renal function. Seven subjects received a 10-mEq sodium diet. At the time of arteriography, arterial blood pressure, pulse rate, cardiac output, renal blood flow, and arterial and renal venous renin activity were measured before and 6-20 minutes after the intravenous administration of propranolol (9-18 mjg/kg). Average renin secretion rate in the salt-depleted subjects fell from 367 +/- 80 (SEM) U/ml per 100 g/min to 122 +/- 51 U/ml per 100 g (P=0.03) and renal plasma flow fell from 189 to 155 ml/min per 100 g (P = 0.018). We also found that in the salt-loaded subjects, renal plasma flow fell from 213 to 184 ml/min per 100 g (P = 0.025), whereas renin secretion did not change significantly in either group. We conclude that propranolol rapidly blocks renin release despite circulatory changes which ordinarily constitute a stimulus for renin secretion, i.e., renal vasoconstriction and reduced renal blood flow.     

Hypertension associated with early stage kidney disease. Complementary roles of circulating renin, the body sodium/volume state and duration of hypertension

Interrelations among blood pressure, exchangeable sodium, blood volume and plasma renin activity were studied in 40 normal subjects and in 40 patients with early stage kidney disease (mean plasma creatinine, 2 mg/100 ml). Findings in eight normotensive patients did not differ significantly from those in normal subjects. However, 32 hypertensive patients showed increases (p less than 0.05) in mean exchangeable sodium and in the products of the logarithm of plasma renin activity and exchangeable sodium or blood volume. In normal subjects, blood pressure did not correlate with any of the parameters measured. In the patients, it correlated significantly (p less than 0.05) with duration of hypertension (r = 0.70), exchangeable sodium (r = 0.34) and with sodium-renin (r = 0.38) or volume-renin (r = 0.30) products, but not with blood volume or circulating renin individually. Multiple regression analysis with blood pressure as a dependent variable, and duration of hypertension and the sodium-renin or volume-renin products as independent variables, revealed correlation coefficients of 0.77 and 0.76, respectively. These findings suggest that hypertension accompanying early stage kidney disease may depend at least partly on subtle abnormalities in the sodium volume-renin feedback mechanism as well as on a factor related to the duration of preexisting hypertension.     

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.     

Aldosterone and renin in liver cirrhosis with ascites

Supine plasma aldosterone and plasma renin activity were determined in patients with cirrhosis of the liver and ascites (n = 10). Most of the patients initially showed an increase in plasma aldosterone and plasma renin activity. However, values within the normal range were observed (plasma aldosterone, n = 3; plasma renin activity, n = 4). In the ascitic fluid renin activity could not be detected, whereas aldosterone concentrations correlated significantly with the respective plasma levels (r = 0.8, p less than 0.01). During therapy with spironolactone alone (n =2) or in combination with furosemide (n = 4), diuresis and natriuresis showed no correlation with changes in plasma aldosterone and/or plasma renin activity. Our results suggest that other factors than renin and aldosterone secretion may be important in the formation of ascites in patients with cirrhosis of the liver. In addition, the inverse correlation between mean arterial blood pressure and plasma renin activity (r = -0.65, p less than 0.05) found in our patients supports the assumption that the increase in renin secretion is probably induced by changes in (renal) hemodynamics.     

Mechanism of the interaction of propranolol and a potent vasodilator antihypertensive agent - minoxidil

A study, using non-invasive techniques, was carried out in ten patients with essential hypertension to examine the mechanism of the hypotensive effect of propranolol when used in combination with a potent vasodilator antihypertensive - minoxidil. The hypotensive effect of minoxidil, a mean (+/- SEM) decrease of 42.4 +/- 4.3 mm Hg, was accompanied by a marked increase in heart rate, cardiac index and plasma renin activity and a significant decrease in total peripheral resistance, limb vascular resistance and pre-ejection period. Addition of propranolol further reduced mean arterial pressure by an average of 12.9 +/- 2.0 mm Hg. Propranolol returned cardiac index to control values and total peripheral resistance index rose but not to control levels. Plasma renin activity was significantly reduced by propranolol. By multiple regression analysis no correlation was found between propranolol-induced decrease in mean arterial pressure and changes in cardiac index, total peripheral resistance index or plasma renin activity. Quantitatively, the reduction in cardiac index observed probably accounted for the hypotensive effect of propranolol. The role of plasma renin activity reduction in the hypotensive effect of propranolol in this situation remains to be clarified. The findings in the present study were consonant with the known actions of vasodilator antihypertensive agents and propranolol and indicate the applicability of non-invasive methodology to the investigation of cardiovascular drugs in man.     

The hypertension of autonomic failure and its treatment

We studied the incidence and severity of supine hypertension in 117 patients with severe primary autonomic failure presenting to a referral center over a 9-year period. Patients were uniformly characterized by disabling orthostatic hypotension, lack of compensatory heart rate increase, abnormal autonomic function tests, and unresponsive plasma norepinephrine. Fifty-four patients had isolated autonomic impairment (pure autonomic failure). Sixty-three patients had central nervous system involvement in addition to autonomic impairment (multiple-system atrophy). Patients were studied off medications, in a metabolic ward, and on a controlled diet containing 150 mEq of sodium. Fifty-six percent of patients had supine diastolic blood pressure > or =90 mm Hg. The prevalence of hypertension was slightly greater in females (63%) than in males (52%). Potential mechanisms responsible for this hypertension were investigated. No correlation was found between blood volume and blood pressure. Similarly, plasma norepinephrine (92+/-15 pg/mL) and plasma renin activity (0.3+/-0.05 ng/mL per hour) were very low in the subset of patients with pure autonomic failure and supine hypertension (mean systolic/diastolic pressure, 177 +/- 6/108 +/- 2 mm Hg, range 167/97 to 219/121). Supine hypertension represents a challenge in the treatment of orthostatic hypotension. We found these patients to be particularly responsive to the hypotensive effects of transdermal nitroglycerin. Doses ranging from 0.025 to 0.1 mg/h decreased systolic blood pressure by 36+/-7 mm Hg and may effectively treat supine hypertension overnight, but the dose should be individualized and used with caution.     

The effect of minoxidil on blood pressure and plasma renin activity in patients with essential and renal hypertension

The effect of the new vasodilator, minoxidil, on blood pressure and plasma renin activity was studied in 21 hypertensive patients: 12 patients with essential and 9 with renal hypertension. The average maximum dosage of minoxidil was 27.9 +/- 6.0 mg/day (M +/- SD). Average duration of treatment was 84.5 days. During the observation period the average systolic blood pressure fell from 195 +/- 18 to 159 +/- 7 mm Hg (M +/- SD), and the mean diastolic blood pressure fell from 120 +/- 8.3 to 92.5 +/- 8 mm Hg (p less than 0.01). These patients had been treated earlier with other antihypertensive agents, such as reserpine, saluretics, hydralazine, alpha-methyldopa, and clonidine, without any significant reduction in blood pressure. Before treatment, plasma renin activity after resting was 59 +/- 6.4 ng/ml/16 h (M +/- SE) and after saluretics and orthostasis 89 +/- 12.7 ng/ml/16 h. After treatment, the decline in renin value after resting was statistically significant: 42.7 +/- 3.3 ng/ml/16 h (p less than 0.05), and the stimulated renin had fallen to 70 +/- 3.4 ng/ml/16 h (p greater than 0.1). A comparison of the renin stimulation values of patients with renal hypertension also revealed a significant reduction (p less than 0.01). Side effects which appeared at a daily dose of 15 to 30 mg consisted mainly of tachycardia and fluid retention and could be controlled by the administration of propranolol and chlorthalidone. In 5 women and in 1 man was observed a cosmetically disturbing, reversible hypertrichosis. Orthostatic hypotension was observed in one patient. Minoxidil is an effective antihypertensive agent. However, because of its side effects, it generally must be administered with beta-receptor blocking agents and saluretics. It is possible that its blood pressure lowering effect is due, at least in part, to a suppression of the plasma renin activity.     

Renin-specific antibody for study of cardiovascular homeostasis

Antiserum specific for purified canine renal renin was used to inhibit this enzyme in trained, conscious dogs. The antiserum did not affect blood pressure in sodium-replete dogs but decreased plasma renin activity and blood pressure in sodium-depleted animals. The antiserum also reduced blood pressure to control levels concomitant with suppression of plasma renin activity in uninephrectomized dogs with acute renovascular hypertension. These observations establish the role of the renin-angiotensin system in the maintenance of blood pressure in the sodium-depleted state as well as in the initiation of renovascular hypertension.     

A delayed suppression of the renin-aldosterone axis following saline infusion in human hypertension

The purpose of this study was to compare the acute suppressibility of the renin-angiotensin-aldosterone (RAA) axis in normotensive (n = 23) and essential hypertensive (n = 62) subjects. Only those hypertensive subjects with normal plasma renin activity (PRA) levels (sodium restricted, upright) were included in the study. Acute suppression of the RAA axis was determined by measuring PRA, plasma angiotensin II (A II), and plasma aldosterone (PA) at frequent intervals during the infusion of isotonic saline (500 ml/hour for 6 hours). Although all parameters fell significantly from control levels by 20-30 minutes in the normotensive subjects, we found that 60% of the hypertensive subjects showed no significant decline in PRA or PA until 120-240 minutes after beginning the infusion. The other hypertensive subjects showed normal RAA suppression. In addition, while there were no significant differences between the three groups in control PRA or PA levels, we found that the PA levels from 30 to 240 minutes during the saline were significantly higher (P less than 0.01) in the hypertensive subjects with delayed suppression. That there were two distinct populations in the hypertensive group was suggested by the bimodality of the frequency response curve, with peaks occurring at 30 and 240 minutes. These studies indicate an abnormality in the acute suppression of the RAA axis in a substantial proportion of subjects with normal renin essential hypertension. Since previous studies in normal subjects have reported that the early phase of response to saline infusion is related to the sodium ion per se and not to intravascular volume expansion, we have come to the conclusion that the present data are consistent with the hypothesis that the delayed suppression hypertensive group has a diminished ability to respond to the sodium ion.     

The molecular genetics of pancreatic cancer

Exaggerated blood pressure (BP) response to exercise in normotensive subjects is considered as a predictor of future hypertension. The aim of the study was to find out whether elevated BP response to exercise is associated with any other haemodynamic, metabolic or hormonal abnormalities. Abnormal BP response to exercise, i.e. systolic BP (SBP) > 200 mmHg at 150 W or lower workload, was found in 37 out of 180 normotensive, male students, aged 20-24 years. Fifteen students with elevated exercise BP (group E) volunteered for further examinations. Their resting and ambulatory BP showed high normal values. Eight of them had a family history of hypertension. Four subjects met the criteria of cardiac hypertrophy. Significant correlations were found between exercise SBP and left ventricular mass index, average 24 h and daytime SBP recordings. In comparison with normal subjects of the same age (group N, n = 13), those from group E did not differ in body mass index, plasma lipid profile, fasting glucose, insulin and catecholamine (CA) concentrations, but had increased erythrocyte sodium content, slightly elevated plasma renin activity and cortisol level. During exercise, E subjects showed greater cardiac output (CO) increases with normal heart rate, total peripheral resistance (TPR) and plasma CA. There were no significant differences between groups in haemodynamic and plasma CA responses to posture change from supine to standing. Glucose ingestion (75 g) caused smaller increases in CO and smaller decreases in TPR in E than in N subjects without differences in BP, blood glucose plasma insulin and CA. It is concluded that young normotensive men with exaggerated BP response to exercise show some other characteristics that may be considered as markers of predisposition to hypertension or factors promoting the development of hypertension.