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Biomedical subjects

V Mooser

Publications and source records attributed to V Mooser.

At least 55 records · Page 3Linked to original sources
PubMed1991

Changes in cardiac angiotensin converting enzyme after myocardial infarction and hypertrophy in rats.

1. Cardiac angiotensin-converting enzyme (ACE) is localized in high concentration in cardiac valves, coronary vessels, right and left atrium and right and left ventricle. 2. Cardiac ACE is functionally active in converting angiotension I to angiotensin II. 3. The level of cardiac ACE measured by radioinhibitor binding or by quantitative in vitro autoradiography was greatly increased after experimental myocardial infarction in the rat. The increase was greatest in the fibrous scar tissue of the free left ventricular wall infarct, but there were also significant increases in the ACE concentration in the four chambers of the heart. 4. Treatment with enalapril for 4 weeks following coronary ligation inhibited cardiac ACE, including the high levels found in the scar in the left ventricular free wall. 5. There was a close relationship between the systolic blood pressure and left ventricular mass in several models of experimental hypertension, despite varying degrees of activation of the renin-angiotensin system. However no relationship between the degree of left ventricular hypertrophy and changes in cardiac ACE could be determined. 6. Inhibition of cardiac ACE may contribute to the beneficial effect of ACE inhibitors in cardiac hypertrophy and remodelling, and may play a part in the cardioprotective role of ACE inhibitor.

Animals↗
PubMed1991

Reduction in left ventricular mass in normotensive and spontaneously hypertensive rats given enalapril.

1. To test the hypothesis that the reduction of left ventricular weight (LVW) observed during angiotensin-converting enzyme (ACE) inhibition in rats is mainly a response to decreased cardiac load, the effect of enalapril on LVW and blood pressure (BP) in normotensive Sprague-Dawley (SD) and in spontaneously hypertensive rats (SHR) was compared. 2. Enalapril decreased BP by 10% in SD rats and 21% in SHR; and LVW by 6% in SD rats and 12% in SHR. A close linear correlation between BP and LVW was observed in SD (r = 0.65, n = 24, P less than 0.001) and SHR (r = 0.92, n = 15, P less than 0.001). 3. The effect of enalapril on LVW, when related to BP, was almost identical in SD and SHR, as the average reduction of LVW (microgram/g of bodyweight) per mmHg was 7.7 +/- 1.9 versus 7.5 +/- 0.9 in SD and SHR respectively. 4. These data constitute additional evidence to support the view that, at least under ACE inhibition, reduction in LVW is mainly due to the fall in BP and the decreased cardiac load.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Characterization of monoclonal antibodies to a rat liver vasopressin receptor.

1. Balb/c mice were immunized against a vasopressin binding protein purified from rat liver. The hybrids produced from two cell fusions were screened against this receptor. Three hybrids were selected, cloned and expanded in serum-free media. The monoclonal antibodies (MoAb) secreted by these three hybrids were of the subclass IgM and were able to immunoprecipitate [125I]-labelled purified receptor. 2. All three MoAb bound to the purified solubilized receptor, crude liver and kidney membranes in a concentration-dependent manner. However, the binding of MoAb to the membranes did not inhibit the binding of [125I]-[d(CH2)5,Sar7]AVP, a selective V1 receptor radioligand, to the liver membrane-bound receptor. 3. These results suggest that the three MoAb recognize epitopes on the V1 receptor which are not denatured by solubilization, but are common to both rat liver and kidney membranes.

Animals↗
PubMed1991

Evaluation of arterial compliance-pressure curves. Effect of antihypertensive drugs.

A new high-precision ultrasonic device was developed to determine noninvasively arterial compliance as a function of blood pressure. Because of the nonlinear elastic properties of arterial walls, measurements of compliance can be appropriately compared only if obtained over a range of pressures. This apparatus was used to evaluate in a double-blind, parallel fashion the effect of three different antihypertensive drugs and of a placebo on radial artery compliance. Thirty-two normotensive volunteers were randomly allocated to an 8-day, once-a-day oral treatment with either a placebo, 100 mg atenolol, 20 mg nitrendipine, or 20 mg lisinopril. Blood pressure, heart rate, radial artery diameter, and arterial compliance were measured immediately before as well as 6 hours after dosing on the first and last days of the study. On the eighth day of administration, within 6 hours after dosing, lisinopril induced an acute increase in radial artery diameter, from 2.99 +/- 0.06 to 3.28 +/- 0.09 mm (mean +/- SEM, p less than 0.01). The compliance-pressure curve was shifted upward on day 1 (p less than 0.01) as well as on day 8 (p less than 0.05). None of the other drugs induced any significant modification of these parameters. Arterial compliance has a strong nonlinear dependency on intra-arterial pressure and therefore has to be defined as a function of pressure. Antihypertensive drugs acting by different mechanisms may have different effects on the mechanical properties of large arteries.

Adrenergic beta-Antagonists↗
PubMed1990

Reactive hyperreninemia is a major determinant of plasma angiotensin II during ACE inhibition.

The new ACE inhibitor trandolapril was administered to normal volunteers at daily doses of 0.5, 2, and 8 mg for 10 days. Twenty-one volunteers, aged 21-30 years, were included in the study. To randomly selected groups of seven subjects, each dose was administered in a single-blind fashion. None of the doses induced a consistent fall in blood pressure. Angiotensin-converting enzyme activity (ACE) was measured in vitro using three different synthetic substrates (i.e., Hip-Gly-Gly, Z-Phe-His-Leu, or angiotensin I). Although the degree of ACE inhibition assessed with the three methods varied widely, all methods clearly indicated dose-dependent ACE inhibition. These in vitro results were confirmed by measuring ACE inhibition in vivo using the ratio of plasma angiotensin II (ANG II) to blood angiotensin I (ANG I). The dose-dependent ACE inhibition was paralleled by a dose-dependent rise in active renin and blood angiotensin I levels, most evident on day 10. In contrast, plasma ANG II levels on day 10 were not different whether the volunteers received 0.5 or 8 mg trandolapril. Thus, whereas increasing doses of this new ACE inhibitor progressively enhanced the blockade of ACE activity, this was not reflected by additional reductions of plasma ANG II levels. The progressive enhancement of ACE inhibition seemed to be offset by the accentuation of the compensatory rise in renin and ANG I, which was still partially converted to ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Caffeine-induced diuresis and atrial natriuretic peptides.

After a single-blind, randomized, cross-over protocol using decaffeinated coffee in a control experiment, the effect of an oral 250-mg caffeine dose on plasma immunoreactive atrial natriuretic peptide (ANF) was assessed in eight healthy students who had been on a methylxanthine-free diet for 1 week. One to 2 h after caffeine ingestion, both systolic blood pressure (SBP) and diastolic BP (DBP) increased by 12 mm Hg while heart rate (HR) also tended to increase. An increase in diuresis and in urinary sodium, potassium, and osmol excretion was observed within 1 h. Decaffeinated coffee induced no change in any of these parameters. Plasma epinephrine (EPI) increased gradually from 16.6 +/- 3.2 pg/ml (mean +/- SEM) to 45.1 +/- 7.9 pg/ml within 2 h after caffeine ingestion, but did not change after decaffeinated coffee (p less than 0.001). Plasma norepinephrine (NE), renin activity (PRA), aldosterone, and vasopressin remained unchanged. Plasma ANF was measured by radioimmunoassay (RIA) using an extremely sensitive antiserum (Kd = 10(-12) M) after rapid and virtually complete (90-103%) extraction from plasma. In 0.2 ml plasma, the theoretical detection limit is 1.1 fmol/ml. Normal plasma ANF concentrations in supine subjects were 17.9 +/- 8.1 fmol/ml (mean +/- SD) and 11.0 +/- 3.3 fmol/ml in subjects in the upright position. Plasma ANF levels were not affected by coffee drinking. In conclusion, by using a new and sensitive assay for plasma ANF, we did not find that caffeine-induced diuresis is mediated by ANF.

Adult↗
PubMed1990

Reduced V1 vasopressin binding in the rat nucleus solitarii after nodose ganglionectomy.

1. Anaesthetized male Sprague-Dawley rats underwent unilateral nodose ganglionectomy or sham operation. 2. One week later hindbrain V1 vasopressin binding site density was assessed by in vitro autoradiography with the selective V1 antagonist radioligand [125I] [d(CH2)5, Sar7]AVP. 3. Specific binding was observed in the nodose ganglion, nucleus tractus solitarius (NTS), area postrema, and inferior olive. Only binding in the medial subnucleus of the NTS was reduced by ipsilateral nodose ganglionectomy. 4. These findings are consistent with V1 vasopressin receptors occurring presynaptically on vagal primary viscerosensory afferent fibres. 5. Such receptors may be involved in the effect of AVP on blood pressure and/or the baroreflex.

Animals↗
PubMed1990

Determinants of angiotensin II generation during converting enzyme inhibition.

The reaction of the renin-angiotensin system to acute angiotensin converting enzyme inhibition was investigated in a single-blind, crossover study in nine normal volunteers receiving two out of three regimens in random order: the new converting enzyme inhibitor benazepril (20 mg once or 5 mg four times at 6-hour intervals) or enalapril (20 mg). Plasma converting enzyme activity, drug levels, angiotensin I and angiotensin II, active renin, and aldosterone were measured before and 1-4 hours and 14-30 hours after drug intake. Baseline in vitro plasma converting enzyme activity was 97 +/- 15 nmol/ml/min (mean +/- SD) when Hip-Gly-Gly was used as substrate, but with carbobenzoxy-Phe-His-Leu (Z-Phe-His-Leu) or angiotensin I as substrate it was only 20 +/- 4 and 1.7 +/- 0.3 nmol/ml/min, respectively. Discriminating power at peak converting enzyme inhibition was enhanced with the two latter substrates. In vivo converting enzyme activity was estimated by the plasma angiotensin II/angiotensin I ratio, which correlated well with in vitro converting enzyme activity using Z-Phe-His-Leu as substrate (r = 0.76, n = 252). Angiotensin II levels returned to baseline less than 24 hours after drug administration, whereas in vitro and in vivo converting enzyme activity remained considerably inhibited and active renin together with angiotensin I levels were still elevated. A close linear relation was found between plasma angiotensin II and the angiotensin I/drug level ratio (r = 0.91 for benazeprilat and r = 0.88 for enalaprilat, p less than 0.001). Thus, plasma angiotensin II truly reflects the resetting of the renin-angiotensin system at any degree of converting enzyme inhibition. The ratio of plasma angiotensin II to angiotensin I represents converting enzyme inhibition more accurately than in vitro assays, which vary considerably depending on substrates and assay conditions used.

Angiotensin I↗
PubMed1990

Localization of vasopressin binding sites in rat tissues using specific V1 and V2 selective ligands.

Arginine vasopressin (AVP) acts on at least two receptor types, classified on the basis of their second messengers. The V1 receptor acts via mobilization of intracellular calcium through phosphatidylinositol hydrolysis and influences blood pressure and hepatic glycogenolysis. The V2 receptor acts via cAMP through activation of adenylate cyclase and causes antidiuresis. Previous studies of the different AVP receptors have been hampered by the use of nonselective radioligands, such as [3H]AVP (which binds to all types of V1 and V2 receptors, certain oxytocin receptors, and neurophysins) as well as the difficulty of measurement of second messengers. This paper describes the use of selective V1 and V2 radioligands with in vitro autoradiography to study V1 and V2 binding sites in rat tissues. [125I][1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 7-sarcosine] arginine vasopressin ([125I][d(CH2)5,Sarcosine7]AVP), a selective V1 antagonist radioligand, bound to regions of the brain, testis, superior cervical ganglion, liver, blood vessels, and renal medulla. Pharmacological characterization of [125I][d(CH2)5,Sarcosine7]AVP binding was consistent with that expected for binding to V1 receptors. There was no specific binding demonstrable to pituitary, renal glomeruli, gut, heart, spinal cord, ovary, adrenal medulla, or adrenal cortex. [3H]1-deamino [8-D-arginine] vasopressin [( 3H]DDAVP), a potent V2 receptor agonist radioligand, was used to study V2 receptors. Specific binding was only identified in the kidney consistent with the known distribution of antidiuretic V2 receptors on renal collecting tubules. No binding was demonstrated on endothelium or liver where DDAVP might influence clotting factor release, nor in the brain, spinal cord, sympathetic ganglia, heart or vascular smooth muscle, regions where DDAVP might cause vasodilatation. These studies demonstrate the use of these radioligands to study V1 and V2 receptors in a variety of tissues. Also, since these ligands are selective they are of particular use to study the different receptor subtypes in tissues where V1 and V2 receptors coexist, such as in the kidney.

Animals↗
PubMed1990

Modulation of the renin-angiotensin system by atrial natriuretic peptide.

Many hormonal systems are involved in salt homeostasis and blood pressure control, including the renin-angiotensin-aldosterone system, the kallikrein-kinin system, and atrial and brain natriuretic peptides. Many of these hormonal peptides have actions both in the central nervous system and the periphery that are complementary. There is also increasing evidence that many of them may act as both circulating endocrine systems as well as local paracrine autocrine systems. The atrial natriuretic peptides may be viewed as endogenous inhibitors of the renin-angiotensin system. Angiotensin-converting enzyme (ACE) and renin inhibitors have provided important information on the role of the renin-angiotensin system in physiological and pathophysiologic states. The development of specific atriopeptidase inhibitors, kinin antagonists, and kallikrein inhibitors offer the same promise for these systems.

Animals↗
PubMed1989

Effect of cold pressor test on the internal diameter of the radial artery.

The aim of this study was to investigate in normal subjects the effect of a cold pressor test on the caliber of the radial artery, a muscular artery of medium size. The internal diameter of this artery was measured continuously using a recently developed ultrasonic device. Immersion of one hand in ice water for two minutes increased blood pressure from 115/75 +/- 3/2 (Mean +/- SEM) to 136/90 +/- 6/2 mm Hg (P less than .001) and decreased the internal diameter of the radial artery from 2.82 +/- 0.12 to 2.60 +/- 0.09 mm (P less than .01). These data therefore indicate that the vasoconstriction induced by the cold pressor test involves not only arterioles, but also medium-size arteries.

Adolescent↗
PubMed1989

Correlation between plasma concentration of cilazapril and haemodynamic and hormonal effects in healthy man.

1. The haemodynamic and humoral effects of cilazapril, a new angiotensin converting enzyme (ACE) inhibitor, were evaluated in normotensive healthy volunteers. 2. Single oral doses of 1.25, 2.5, 5 and 10 mg of cilazapril inhibited ACE by greater than or equal to 90% and induced the expected pattern of changes of the renin-angiotensin-aldosterone-system. 3. Cilazapril had a long duration of action, since some ACE inhibition was still present 72 h after drug intake. 4. Cilazapril administered intravenously at doses of 5 and 20 micrograms kg-1 for 24 h did not produce any significant effects. 5. During repeated administration of cilazapril for 8 days, no accumulation of cilazaprilat was observed and the clinical tolerance was excellent. 6. In normal volunteers, cilazapril administered orally acts as a potent inhibitor of converting enzyme.

Administration, Oral↗
PubMed1989

Bolus injections of synthetic atrial natriuretic peptide in patients with chronic renal failure or nephrotic syndrome.

The diuretic and natriuretic responses to exogenous synthetic atrial natriuretic peptide (ANP) were evaluated in patients with chronic renal failure (CRF) or nephrotic syndrome (NS). Patients were studied after an oral water load (8 ml/kg in CRF and 20 ml/kg in NS patients). A short intravenous bolus of either a placebo or ANP was administered when urine output was stable. In each group of patients, three doses of ANP were injected at 24 h intervals, i.e., 1.0, 1.5, and 2.0 micrograms/kg in the CRF and 1.0, 1.5, and 3.0 micrograms/kg in the NS group. Blood pressure and heart rate were monitored throughout the study and urinary volume and electrolyte excretion were measured every 20 min up to 3 h after the bolus. An acute and transient fall in blood pressure was observed immediately after the ANP injection. It was more pronounced in CRF than in NS patients. In CRF patients, ANP caused only a slight increase in urinary volume (13.5-44% over baseline) but a significant increase in urinary sodium excretion (45-114% over baseline). In NS patients, significant increases in both urine volume (60-105%) and sodium excretion (149-248%) were also found. In these latter patients, the renal response to ANP appeared to be better preserved. The hemodynamic and renal changes induced by ANP occurred mainly during the first 20 min following the ANP administration, when the peak plasma ANP levels were obtained. However, no clear dose-response effect could be evidenced in either group with the three doses of ANP chosen in this study.

Adult↗
PubMed1989

Effects of smoking and physical exercise on platelet free cytosolic calcium in healthy normotensive volunteers.

Platelet free cytosolic calcium (PFCC) was measured in 21 healthy volunteers before and after cigarette smoking or physical exercise. The aim was to investigate whether acute blood pressure changes and increases in circulating levels of catecholamines and vasopressin modify PFCC. PFCC was determined using the Quin-2 method. Following cigarette smoking, significant increases in blood pressure, heart rate, plasma epinephrine (35 +/- 18 pg/ml before versus 51 +/- 31 pg/ml after smoking, P less than 0.05, mean +/- s.d.) and vasopressin levels (0.8 +/- 0.3 pg/ml before and 4.2 +/- 4.1 pg/ml after smoking, P less than 0.001) were observed. However, despite these acute hormonal and hemodynamic changes, PFCC remained stable at 156 +/- 55 nmol/l prior to the study and 157 +/- 29 nmol/l and 156 +/- 38 nmol/l at 20 and 80 min post-smoking, respectively. Acute physical exercise led to an increase in heart rate and systolic blood pressure but to a decrease in diastolic pressure. Moreover, a marked increase in plasma norepinephrine levels was observed after exercise (213 +/- 71 pg/ml before versus 747 +/- 501 pg/ml after exercise, P +/- 0.001). Again, PFCC was stable at 185 +/- 56 nmol/l at baseline versus 188 +/- 51 nmol/l at 20 min and 155 +/- 26 nmol/l at 80 min after exercise. These results therefore demonstrate that PFCC is not influenced acutely either by blood pressure increases, or by elevations in circulating catecholamine and vasopressin concentrations.

Adult↗
PubMed1988

Non-invasive measurement of internal diameter of peripheral arteries during the cardiac cycle.

An ultrasonic device was developed for continuous monitoring of the internal diameter of human peripheral arteries. The diastolic internal diameter of the radial artery measured in 10 supine normotensive subjects averaged 2.36 +/- 0.12 mm (mean +/- s.e.) and the change in diameter during the pulse wave was 0.037 +/- 0.003 mm. It was surprising to find that when the transducer was used to apply pressure on the radial artery, the difference between the systolic and the diastolic diameter was significantly increased while the diastolic diameter was reduced. This method therefore allows continuous, accurate and non-invasive measurement of the internal diameter of the human radial artery.

Arteries↗
PubMed1988

Infusion of atrial natriuretic peptide to patients with congestive heart failure.

Atrial natriuretic peptides (ANP) exert vasodilating and natriuretic actions. The present study was undertaken to test the effect of low dose infusions of synthetic ANP on hemodynamic and humoral variables of patients with severe heart failure. Eight patients, aged 26 to 71 years, with severe congestive heart failure due to ischemic heart disease or idiopathic dilated cardiomyopathy were included in the study. Synthetic human (3-28) ANP was infused at doses ranging from 0.5 to 2 micrograms/min for up to 3 h. Pulmonary capillary wedge pressure fell from 24 +/- 1 to 16 +/- 2 mm Hg (mean +/- SEM) (p less than 0.01) and cardiac index tended to rise from 2 +/- 0.2 to 2.3 +/- 0.2 L/min/m2 (NS), while blood pressure and heart rate did not change. One patient experienced a marked drop in pulmonary capillary wedge and arterial blood pressure that necessitated the administration of saline. ANP infusion did not alter plasma renin activity or plasma aldosterone, norepinephrine, or vasopressin levels. It decreased plasma epinephrine levels from 0.472 +/- 0.077 to 0.267 +/- 0.024 nmol/L (p less than 0.05). Plasma ANP levels were markedly elevated in all patients before initiating the infusion. They had no predictive value for the hemodynamic response to exogenous ANP. No correlation was observed between the hemodynamic effects of ANP and those induced by the subsequently administered converting enzyme inhibitor captopril, which seemed to improve cardiac function more consistently.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗