Plasma endothelin-1 levels during transient acute myocardial ischaemia in men: effects of coronary revascularization

The endothelium-derived peptide endothelin-1 (ET-1) was evaluated in 14 male patients [mean age 52.74 years (SEM 1.10)] affected by coronary artery disease during a bicycle electrocardiographic stress test and dipyridamole echocardiogram. Both tests were performed before and after coronary revascularization. Fourteen healthy male subjects served as controls [mean age 53.21 years (SEM 1.63)]. Baseline plasma endothelin-1 levels were higher (P < 0.0001) in ischaemic patients [1.81 pg mL-1 (0.15, n = 14)] than in control subjects [0.61 pg mL-1 (0.03, n = 14)], but did not increase with exercise in both groups. Similar results were obtained with dipyridamole infusion. Endothelin-1 levels significantly decreased after coronary revascularization [before: mean 1.81 pg mL-1 (SEM 0.15, n = 14); after: mean 1.16 pg mL-1 (SEM 0.11), P < 0.002], without changes in the peptide response to both tests. In conclusion, elevated plasma endothelin-1 concentrations were found in patients with stable angina compared with non-ischaemic subjects. No changes were observed during exercise or dipyridamole infusion in both groups. Coronary revascularization was followed by a significant decrease in plasma endothelin-1 levels.     

Gene therapy with bilirubin-UDP-glucuronosyltransferase in the Gunn rat model of Crigler-Najjar syndrome type 1

PURPOSE: The purpose of this study was to investigate the relationship between training-induced alterations in plasma volume (PV) and changes in fluid and electrolyte regulatory hormones during prolonged exercise. METHODS: Seven male subjects (VO2peak 49.2 +/- 2.4 mL.kg-1.min-1, X +/- SE) performed a cycling test before (C) and after (T) 6 d of training and after 6 d of detraining (DT). Training was conducted for 2 h.d-1 at 68% VO2peak at a room temperature between 26-28 degrees C. The 60-min exercise challenge included 20 min at 50%, 65%, and 75% VO2peak workloads. RESULTS: Training resulted in a calculated 13.8 +/- 1.6% PV expansion (P < 0.05) which recovered to C levels with DT (1.8 +/- 2.3%, P > 0.05). Compared with that at C, training resulted in a reduction of aldosterone (ALDO) concentration at all exercise intensities (P < 0.05) which normalized to C levels with DT. With T, epinephrine (EPI) concentrations were reduced at the highest power output only (365 +/- 51 vs 113 +/- 22 pg.mL-1; P < 0.05) and returned to C levels with DT. Arginine vasopressin (AVP) concentrations were also reduced at the highest workload only (20.2 +/- 3.2 pg.mL-1 vs 10.4 +/- 0.7 pg.mL-1; P < 0.05) and remained depressed after DT (11.8 +/- 1.3 pg.mL-1; P < 0.05). Atrial natriuretic factor (ANF) and norepinephrine (NOREPI) were not affected by T or DT. CONCLUSIONS: The results suggest that concentrations of ALDO, and to a lesser extent EPI, during exercise are related to PV levels, whereas ANF and NOREPI concentrations are not. AVP concentrations are related to other adaptive factors, the effects of which persist for a longer time course than do PV changes.     

Anthropometric measurements and vertebral deformities. European Vertebral Osteoporosis Study (EVOS) Group

BACKGROUND: Plasma levels of B-type natriuretic peptide (BNP) are markedly increased in patients with heart failure and acute myocardial infarction. The changes in plasma BNP levels in the treatment of acute myocardial infarction with angiotensin-converting enzyme inhibitors have not been examined well. This study was designed to examine the effects of early angiotensin-converting enzyme inhibitor therapy on plasma BNP levels in patients with acute myocardial infarction. METHODS AND RESULTS: We measured the plasma levels of B-type natriuretic peptide over the time course for 2 weeks in 30 patients with acute myocardial infarction in whom either imidapril (n = 15) or placebo (n = 15) was given at random immediately after admission. Plasma BNP levels increased and reached a peak of 192 +/- 28 pg/ML 16 hours after administration; thereafter, the levels decreased and then again increased, forming the second peak of 217 +/- 38 pg/ML on the fifth day (biphasic pattern). On the other hand, plasma BNP levels increased and reached a peak level of 190 +/- 22 pg/ML 16 hours after admission and then decreased from 2 days after admission until the second week in the imidapril group (monophasic pattern). Left ventricular ejection fraction measured in the second week was significantly higher in the imidapril group than in the control group (62.2 +/- 1.1% vs 51.2 +/- 3.6%, P < .01). CONCLUSION: It is concluded that plasma BNP levels followed a monophasic pattern after imidapril treatment, whereas a biphasic pattern was followed after placebo, and that plasma BNP levels constitute a marker of ventricular dysfunction in the treatment of acute myocardial infarction with angiotensin-converting enzyme inhibitors.     

Hypocalcemic effect of elcatonin in mouse models for humoral hypercalcemia of malignancy

To elucidate the effect of calcitonin on humoral hypercalcemia of malignancy (HHM), we studied the effect of elcatonin, a synthetic eel calcitonin analog, on plasma calcium concentration in hypercalcemic nude mice transplanted subcutaneously with FA-6 pancreas cancer cells and hypercalcemic mice produced by continuous infusion of parathyroid hormone-related peptide (PTHrP). Elcatonin proved to exert a potent hypocalcemic effect in either model for hypercalcemia. The effect reached peaks at 2 hr after its administration, and it was no longer detected at 24 hr. The dose-dependent effects of a single administration of elcatonin were studied in the FA-6 tumor-bearing mice: the hypocalcemic effect of elcatonin at 1-2 hr after administration was dose-relatedly augmented. The effect of daily administration of elcatonin was further studied in the FA-6 tumor-bearing mice: 5-Day daily administration of elcatonin was not accompanied by reduction in its hypocalcemic effect. Moreover, it was suggested that higher the efficacy of elcatonin, the higher were the plasma calcium concentrations in the tumor-bearing mice. These results indicated that elcatonin exerts an immediate hypocalcemic effect even on models for acute and severe hypercalcemia such as FA-6 tumor-bearing mice, that this hypocalcemic effect became more potent depending on their elevation of plasma calcium concentration, and that elcatonin exerts a hypocalcemic effect even on a model for hypercalcemia due to PTHrP, a presumable causative substance of HHM.     

Influence of physiologic hyperglucagonemia on basal and insulin-inhibited splanchnic glucose output in normal man

To evaluate the effects of physiologic hyperglucagonemia on splanchnic glucose output, glucagon was infused in a dose of 3 ng/kg per min to healthy subjects in the basal state and after splanchnic glucose output had been inhibited by an infusion of glucose (2 mg/kg per min). In the basal state, infusion of glucagon causing a 309 +/- 25 pg/ml rise in plasma concentration was accompanied by a rapid increase in splanchnic glucose output to values two to three times basal by 7-15 min. The rise in arterial blood glucose (0.5-1.5 mM) correlated directly with the increment in splanchnic glucose output. Despite continued glucagon infusion, and in the face of stable insulin levels, splanchnic glucose output declined after 22 min, returning to basal levels by 30-45 min. In the subjects initially receiving the glucose infusion, arterial insulin concentration rose by 5-12 muU/ml, while splanchnic glucose output fell by 85-100%. Infusion of glucagon causing an increment in plasma glucagon concentration of 272 +/- 30 pg/ml reversed the inhibition in splanchnic glucose production within 5 min. Splanchnic glucose output reached a peak increment 60% above basal levels at 10 min, and subsequently declined to levels 20-25% below basal at 30-45 min. These findings provide direct evidence that physiologic increments in plasma glucagon stimulate splanchnic glucose output in the basal state and reverse insulin-mediated inhibition of splanchnic glucose production in normal man. The transient nature of the stimulatory effect of glucagon on splanchnic glucose output suggests the rapid development of inhibition or reversal of glucagon action. This inhibition does not appear to depend on increased insulin secretio.     

Plasma endothelin and early coronary endothelial dysfunction in recipients of a cardiac transplant

Serotonin constricts coronary arteries with endothelial dysfunction, possibly through reduced endothelial release of nitric oxide or enhanced production of constricting factors such as endothelin. Because the plasma levels of this peptide are increased in the early months after cardiac transplantation, we assessed whether a coronary hypersensitivity to the vasoconstrictor effect of serotonin is associated with high plasma endothelin levels. One to 3 months after cardiac transplantation, serotonin (1, 10, or 20 micrograms/min for 2.5 min each) was infused into the coronary circulation in 32 patients. Changes in coronary diameters were determined by quantitative angiography. A > or = 40% reduction in coronary diameter for a dose of serotonin < or = 10 micrograms/min was observed in group A (n = 14) whereas in group B (n = 18), this diameter reduction was never reached even for a 20 micrograms/min infusion of serotonin. Plasma endothelin levels were significantly higher (p < 0.01) in the coronary ostium and coronary sinus in group A, at 23.4 +/- 1.3 pg/ml and 24.9 +/- 0.9 pg/ml versus 12.6 +/- 0.9 pg/ml and 13.8 +/- 1.1 pg/ml, respectively, in group B. These endothelin levels did not significantly change after intracoronary infusion of serotonin. A significant correlation was found between plasma endothelin levels in the coronary ostium and peak coronary constriction (percentage diameter reduction) in both groups (r = 0.77 for group A and r = 0.92 for group B). Thus, early after cardiac transplantation, serotonin-induced coronary constriction is a common finding, and the severity of this abnormality seems to be influenced by plasma endothelin levels.     

Effect of diaspirin cross-linked hemoglobin on endothelin-1 and blood pressure in acute ischemic stroke in man

OBJECTIVE: For almost 50 years it has been known that hemolysed blood can increase blood pressure. Although preclinical studies suggest that this pressor response is due to an interaction of hemoglobin with endothelium-derived vasoactive substances, its mechanism in humans is unknown. We investigated the involvement of endothelin-1 in the blood pressure response to the oxygen carrier diaspirin cross-linked hemoglobin (DCLHb) in stroke patients. DESIGN: In a randomized phase II study, increasing doses of DCLHb (25, 50 and 100 mg/kg, n=8, 8 and 11, respectively) or placebo (n=26) were infused intravenously every 6 h for 72 h to patients with an acute ischemic stroke. Blood pressure and heart rate were measured every 15 min and plasma concentrations of endothelin-1, catecholamines, renin, vasopressin and atrial natriuretic peptide were measured before and 24 and 66 h after the start of the infusions. RESULTS: In the placebo group, mean arterial pressure (MAP) was 112 (109-115) mmHg (mean and 95% confidence interval) at baseline and decreased spontaneously by 11.4 (5.4-17.5) and 12.5 (5.4-19.5) mmHg after 24 and 66 h, respectively. This decrease in MAP was attenuated in patients treated with DCLHb, reaching statistical significance in the highest dose group. The plasma endothelin-1 concentration decreased slightly in the placebo group, from 4.2 (3.1-5.3) pg/ml (median and range) at baseline to 2.4 (1.9-3.7) pg/ml after 24 h (P=0.0044) and 2.8 (1.9-3.7) pg/ml after 66 h (P=0.0042), but increased dose-dependently in response to DCLHb infusion. With the highest dose of DCLHb, the plasma endothelin-1 concentration rose from 4.8 (0.1-7.8) pg/ml at baseline to 21.2 (13.4-53.2) pg/ml after 24 h (P< 0.001) and to 27.6 (11.9-47.8) pg/ml after 66 h (P< 0.001). The increases in the plasma endothelin-1 concentration and in MAP were correlated (r=0.30, P=0.02). Other vasoactive hormones were not affected by the DCLHb infusion. CONCLUSIONS: Infusion of DCLHb in patients with acute ischemic stroke was associated with a dose-dependent increase in plasma endothelin-1 concentration. This may underlie the attenuation by DCLHb of the natural decrease in blood pressure that we observed in these patients.     

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)     

Behavior of plasma levels of endothelin 1 and noradrenaline in patients with stable angina during the cold pressor test

The aim of this study was to evaluate the behaviour of plasma endothelin-1 (ET-1) and norepinephrine (NE) levels in patients with stable angina during a sympathetic stimulation test as the cold pressor test. We enrolled in the study 29 subjects: 14 patients with stable angina (all men, mean age 58.3 +/- 7.3 years) and 15 healthy subjects (all men, mean age 54 +/- 5 years). All patients with stable angina had a stenosis of the coronary arteries (at least 70% of the stenosis in one of the coronary arteries) confirmed by angiography. Before (-15 min; 0 min) during (+2 min) and after the cold pressor test (+5 min, +10 min, +20 min, +30 min) were measured the blood pressure and the heart rate. At the same time were collected venous samples for the ET-1 and NE determination. ET-1 levels increased only in the patients with stable angina (ET-1: O' = 9.8 +/- 3.7 pg/ml; +2' = 11.1 +/- 4.5 pg/ml; +10' = 14.8 +/- 7.1 pg/ml; +20' = 11.6 +/- 5.1 pg/ml; p < 0.05 vs 0', +2'; +20'). The NE levels increased in both groups (NE stable angina: 0' = 105 +/- 31 pg/ml; +2' = 206 +/- 127 pg/ml; +5' = 223 +/- 135 pg/ml; p < .05 vs +2', +5'); (NE healthy subjects 0' = 85 +/- 10 pg/ml; +2' 165 +/- 49 pg/ml; p < 0.05 vs + 2'). In conclusion, our study showed that cold pressor test is a stimulus for the sympathetic system in both groups. The increased levels of ET-1 detected only in the patients with stable angina suggest that this peptide can take part to the pathogenesis of the coronary artery disease.     

Gastrin-releasing peptide-like immunoreactive substance in bronchoalveolar lavage of idiopathic pulmonary fibrosis and sarcoidosis

The neuropeptide gastrin releasing peptide (GRP) is present in the lung, and functions as a modulator of tissue growth and repair in fibrotic processes, or as a modulator of cell movement and differentiation in various inflammatory processes, including granulomatous ones. In idiopathic pulmonary fibrosis (IPF), changes in the bronchoalveolar lavage (BAL) content of GRP can be expected. We measured GRP-like immunoreactive substances (GRP-IS) and another neuropeptide, vasoactive intestinal peptide (VIP)-IS in BAL by enzyme immunoassay. Our results showed a decrease in BAL GRP-IS in patients with IPF (26.5 +/- 5.5 pg.mg-1 protein) and sarcoidosis (35.9 +/- 9.2 pg.mg-1), compared to healthy nonsmokers (63.4 +/- 9.0 pg.mg-1). When data were expressed as pg.ml-1 BAL fluid recovered, a decrease was only seen in IPF, not in sarcoidosis. The levels of VIP-IS in BAL were not different between the groups studied. Increased protein levels in BAL had no correlation with the levels of GRP-IS or VIP-IS in BAL. Furthermore, BAL neutrophil percentages had no correlation with the levels of GRP-IS in BAL of patients with IPF. Using reversed phase high performance liquid chromatography (HPLC), several kinds of GRP-IS were detected in BAL. These findings suggest that the decreased level of GRP-IS in BAL may reflect a loss of GRP-producing cells due to chronic lung injury and fibrosis in patients with IPF.     

Urinary endothelin-like immunoreactivity in patients with cirrhosis

BACKGROUND/AIMS: To investigate a possible relationship between the renal production of endothelin and the presence of renal dysfunction and activation of vasoactive systems in cirrhosis, the urinary excretion and the circulating plasma levels of immunoreactive endothelin (irET) and the plasma levels of vasoactive hormones were measured in 19 healthy subjects, 12 cirrhotic patients without ascites and 39 patients with ascites and different degrees of renal dysfunction. METHODS: The urinary excretion and the circulating levels of irET were assessed after 5 days on a 40 mEq sodium diet and off diuretics. Renal function parameters and the plasma levels of vasoactive hormones were also measured. RESULTS: Patients with and without ascites had similar values of urinary irET as compared with healthy subjects (30+/-3, 31+/-3 and 29+/-2 ng/day, respectively, p>0.10). By contrast, patients with ascites had higher circulating levels of irET (15+/-1.2 pg/ml) than patients without ascites and healthy subjects (11+/-1.6 and 5+/-0.4 pg/ml, p<0.01). In patients with cirrhosis, no correlation was found between urinary irET and circulating irET. Moreover, urinary irET did not correlate with liver tests, serum and urine sodium, glomerular filtration rate or vasoactive substances. Patients with hepatorenal syndrome had similar urinary irET to patients with ascites without hepatorenal syndrome. CONCLUSIONS: Urinary excretion of irET is not increased in cirrhotic patients with ascites and does not correlate with abnormalities in renal function.     

GLP-1 tablet in type 2 diabetes in fasting and postprandial conditions

OBJECTIVE: To examine the absorption of glucagon-like peptide (GLP)-1(7-36) amide from the buccal mucosa of type 2 diabetic patients. Previously, the effects of the peptide have been studied following intravenous and subcutaneous injection. Now, a mucoadhesive, biodegradable buccal GLP-1 tablet (9 mm) containing 119 nmol has been developed as a possible alternative to injection. RESEARCH DESIGN AND METHODS: A total of 10 type 2 diabetic patients received a single tablet under fasting conditions and before a standard meal in this randomized placebo-controlled study. RESULTS: The mean peak GLP-1 concentration was 125.1 pmol/l and occurred 30 min after application. The mean placebo-adjusted area under the curve was 5,334 min pmol/l, consistent with a relative bioavailability of 6% vs. intravenous injection and 42% vs. subcutaneous injection. The half-life of total peptide activity after buccal administration was 17 min. The placebo-adjusted glucose concentrations decreased by 1.4 mmol/l in fasting experiments and by 4.2 mmol/l after a standard mixed meal. In the fasting state at 30 min, plasma insulin increased by 185% and glucagon decreased by 20%, consistent with the increase in plasma GLP-1 concentrations. The peptide exerted a significant insulinotropic effect during meals (calculated as an insulinogenic index, 0-120 min; 84.1 vs. 45.7 in placebo experiments). CONCLUSIONS: Potentially therapeutic plasma levels of GLP-1 were achieved after administration of a single buccal tablet in type 2 diabetic patients. The peptide had a marked glucose-lowering effect during the first 2 h. This new GLP-1 tablet may become a feasible alternative treatment for type 2 diabetic patients, although a more prolonged pharmacokinetic profile is required.     

White cell-reduced red cells prepared by filtration: a critical evaluation of current filters and methods for counting residual white cells

Atrial natriuretic peptide (ANP) is reported to dilate a major coronary artery in both experimental animals and humans. Spasm of a major coronary artery is the cause of variant angina pectoris and can be induced by hyperventilation. The effect of the ANP infusion on anginal attack induced by hyperventilation was studied in patients with variant angina pectoris. The study was performed in the early morning on 3 consecutive days in 11 patients with variant angina pectoris in whom the attacks were reproducibly induced by hyperventilation. On days 1 and 3 (saline solution infusion), and day 2 (ANP infusion), hyperventilation was started 14 minutes after beginning infusion of ANP (0.1 microgram/kg/min) or saline solution for 6 minutes. The attacks were induced in all 11 patients by hyperventilation on days 1 and 3. However, the attacks were not induced in any patient on day 2 of the ANP infusion. The plasma ANP level increased from 33 +/- 7 pg/ml to the peak level of 2,973 +/- 479 pg/ml (p < 0.01) at the end of the ANP infusion, and the plasma level of cyclic guanosine monophosphate (cGMP) increased from 5 +/- 1 pmol/ml to the peak level of 58 +/- 6 pmol/ml (p < 0.01) 5 minutes after the ANP infusion. The plasma levels of ANP and cGMP did not change after hyperventilation on days 1 and 3. It is concluded that the ANP infusion suppresses the attacks induced by hyperventilation in patients with variant angina pectoris, and cGMP is related to the mechanisms of suppression of the attacks.     

Motilin in human milk: identification and stability during digestion

The presence of motilin in human milk and the influence of human milk on the degradation of [125I][Nle13] porcine motilin by gastric and duodenal fluids were investigated. Milk and plasma samples were collected from 14 mothers, and motilin was measured by radioimmunoassay. Plasma levels were 416 +/- 37 pg/mL. In 8 defatted samples the motilin level was 105 +/- 14 pg/mL, in the six others levels were above 1000 pg/mL but dilution curves were non-linear. After solid-phase extraction milk levels were 108 +/- 21 pg/mL in 13 samples, in 1 sample the dilution curve was still non-linear. The stability of motilin after ingestion was studied in vitro by incubating [121I][Nle13] porcine motilin with gastric and intestinal juices obtained from newborns (10 times diluted). Incubations were performed at 37 degrees C at pH 1.8, 3.2 and 5.8 for the gastric fluid and at pH 7.4 for the duodenal fluid. After different times of intervals (5, 10, 20 and 30 minutes) intact motilin was precipitated with trichloroacetic acid and the radioactivity of the supernatant was determined. Motilin was rapidly degraded by gastric juice. The breakdown was greatest at pH 3.2 (74% after 30 minutes) and lowest at pH 5.8 (29%), the pH after milk feeding in neonates. Degradation by intestinal juice at pH 7.4 was also very rapid (77% after 30 minutes). Human milk and BSA inhibited partially the gastric digestion at pH 3.2 (17 and 29%, respectively). Digestion by intestinal juice was not affected by human milk and BSA. These results suggest that digestion of motilin in the stomach may be sufficiently retarded by human milk in the newborn to exert a biological role.     

Stability, tissue metabolism, tissue distribution and blood partition of azosemide

Stability of azosemide after incubation in various pH solutions, human plasma, human gastric juice, and rat liver homogenates, metabolism of azosemide after incubation in 9000 g supernatant fraction of various rat tissue homogenates in the presence of NADPH, tissue distribution of azosemide and M1 after intravenous (i.v.) administration of azosemide, 20 mg kg-1, to rats, and blood partition of azosemide between plasma and blood cells from rabbit blood were studied. Azosemide seemed to be stable for up to 48 h incubation in various pH solutions ranging from two to 13 at an azosemide concentration of 10 micrograms mL-1; more than 93.4% of azosemide was recovered, and a metabolite of azosemide, M1, was not detected. However, the drug was unstable in pH1 solution: 75.8% of azosemide was recovered and 2.16 micrograms mL-1 of M1 (expressed in terms of azosemide) was formed after 48 h incubation in pH 1 solution at an azosemide concentration of 10 micrograms mL-1. Azosemide was stable in both human plasma and rat liver homogenates for up to 24 h incubation at an azosemide concentration of 1 microgram mL-1, and in human gastric juice for up to 4 h incubation at an azosemide concentration of 10 micrograms mL-1. However, all rat tissues studied had metabolic activity for azosemide in the presence of NADPH, with heart having a considerable metabolic activity: approximately 22% of azosemide disappeared and 9.32 micrograms of M1 was formed per gram of heart (expressed in terms of azosemide) after 30 min incubation of 50 micrograms of azosemide in 9000 g supernatant fraction of heart homogenates. The tissue to plasma ratios of azosemide (T/P) were greater than unity only in the liver (1.26) and kidney (1.74); however, M1 showed high affinity for all tissues studied except the brain and spleen when each tissue was collected at 30 min after i.v. administration of azosemide to rats. The equilibrium plasma to blood cell concentration ratios of azosemide were independent of azosemide blood concentrations: the values were 2.78-4.25 at azosemide blood concentrations of 1, 10, and 20 micrograms mL-1 in three rabbits. There was negligible 'blood storage effect' of azosemide, especially at low blood concentrations of azosemide, such as 1 and 10 micrograms mL-1.     

Quantitative and topographical study of retinal ganglion cells in the chameleon (Chameleo chameleon)

The existence of a circadian rhythm of atrial natriuretic peptide (ANP) in humans is controversial. We studied the plasma ANP response to isotonic blood volume expansion in the morning and in the afternoon and its relationship with adrenocorticotropic hormone (ACTH)-cortisol diurnal variation in seven normal subjects. Basal plasma ANP level was similar in the morning (19.6 +/- 2.4 pg/ml) and in the afternoon (21.8 +/- 4.8 pg/ml). The ANP peak obtained with saline infusion (0.9% NaCl, 12 ml/kg) in the morning (49.4 +/- 8 pg/ml) did not differ from that obtained in the afternoon (60.3 +/- 10.1 pg/ml). There was no correlation between the individual mean cortisol and ACTH levels and the ANP peak obtained with saline infusion. These data indicate no diurnal variation in plasma ANP secretion induced by blood volume expansion and no relationship between plasma ANP peak and ACTH-cortisol diurnal variation.     

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.     

Changes of vasoactive peptides and effects of inhaled nitric oxide after pneumonectomy

To clarify the role of vasoactive peptides in the physiologic response to pneumonectomy, we investigated the changes of atrial (A-type) natriuretic peptide (ANP). C-type natriuretic peptide (CNP), and endothelin-1 (ET-1) levels in the lung and blood after pneumonectomy and the effects of inhaled nitric oxide (NO; 5 ppm) after pneumonectomy in beagle dogs. The concentrations of these peptides in the lung and blood were measured by radioimmunoassay. The dogs in group A (n = 10) were observed without NO inhaling after right pneumonectomy, and the dogs in group B (n = 5) were observed with NO inhaling from 120 to 180 min after right pneumonectomy. After the thoracotomy, right lung tissue was resected for the pre-operative histological control. Tissue from the left lung was obtained at 120 min (5 dogs in group A), at 180 min (5 dogs in group A), and after 60 min of NO inhalation (group B) for the post-operative histological material. Peripheral blood was collected from the femoral artery. The pulmonary arterial pressure (PAP) was significantly increased after pneumonectomy, but rapidly decreased to the same level as the pre-operative stage after NO inhalation. Increases of plasma ANP, lung ANP and lung CNP levels occurred after pneumonectomy, while the ET-1 level was unchanged. Inhaled NO rapidly reduced the plasma ANP, lung ANP and lung CNP. These results indicate that both ANP and CNP act to maintain normotensive homeostatic balance in the pulmonary circulation.     

Possible involvement of neuropeptidergic sensory nerves in alopecia areata

Alopecia areata (AA) is a dermatosis involving the sudden occurrence of bald patches on the scalp. Although the aetiology is unknown, experimental data indicate that cutaneous microcirculation plays an important role. The skin is richly innervated by neuropeptidergic sensory nerves that help regulate microvascular circulation. This study shows a reduction of cutaneous levels of substance P and calcitonin gene-related peptide (CGRP) but not of vasoactive intestinal polypeptide in scalp biopsies from patients with AA. Laser-Doppler flowmetry was used to study microcirculation of the scalp. Results indicate that patients with AA have lower basal blood flow and greater vasodilatation following intradermal CGRP injection than control subjects. A vascular hyper-reactivity to vasodilatatory substances such as neuropeptides, probably because of the lack of these substances, is hypothesized.     

Pentavalent technetium-99m-dimercaptosuccinic acid scintigraphy in renal osteodystrophy

OBJECTIVE: To establish whether oxytocin modifies the stimulatory effect of vasoactive intestinal polypeptide (VIP) on prolactin secretion in healthy women. DESIGN: Controlled clinical study. SETTING: Healthy women in an academic research environment. PATIENT(S): Seven healthy women (aged 24-32 years) were tested on the 22nd day of two consecutive normal menstrual cycles. INTERVENTION(S): Vasoactive intestinal polypeptide (4 pmol x kg(-1) x min(-1) in 50 mL of normal saline infused i.v. for 60 minutes) was administered in either the presence or absence of concurrent treatment with oxytocin (2 IU injected plus 0.07 IU/min infused for 60 minutes). MAIN OUTCOME MEASURE(S): Serum prolactin levels. RESULT(S): The administration of VIP induced a significant increase in serum prolactin levels, with a mean peak response 1.6 times higher than baseline at 45 minutes after injection. In the presence of oxytocin, the prolactin response to VIP was significantly higher, with a mean peak response 2 times higher than baseline. CONCLUSION(S): These data suggest that in healthy women, oxytocin facilitates the regulation of the stimulating effect of VIP on prolactin secretion.