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Biomedical subjects

B Waeber

Publications and source records attributed to B Waeber.

At least 325 records · Page 18Linked to original sources
PubMed1986

Lithium infusion to study sodium handling in unanesthetized hypertensive rats.

To investigate renal tubular handling of sodium in various types of experimental hypertension, sodium, lithium, and inulin clearances were measured simultaneously in unanesthetized rats. Fractional excretion of lithium was used as an index of proximal sodium reabsorption. Eight groups of animals, all of the Wistar-Kyoto strain, were studied. Three were hypertensive: spontaneously hypertensive rats (SHR), rats with two-kidney, one clip renal hypertension, and uninephrectomized rats with deoxycorticosterone-salt hypertension. The five normotensive control groups included animals given normal, low, or high dietary sodium loads and rats with reduced renal mass. Fractional excretion of lithium was not influenced by moderate changes of glomerular filtration rate, but was sharply enhanced by sodium loading. Increased blood pressure was associated with enhanced urinary sodium excretion in uninephrectomized deoxycorticosterone-salt hypertensive and two-kidney, one clip hypertensive rats, as a result of decreased distal tubular reabsorption ("pressure natriuresis"). In contrast, SHR showed reduced sodium excretion and decreased fractional excretion of lithium, which suggests that increased sodium reabsorption in the proximal tubule may contribute significantly to the maintenance of hypertension.

Animals↗
PubMed1986

Specific measurement of angiotensin metabolites and in vitro generated angiotensin II in plasma.

Combining high-performance liquid chromatography with radioimmunoassay enabled the precise measurement of different angiotensins and their metabolites in plasma. Peptides were extracted from 2 ml of plasma by reversible adsorption to phenylsilyl-silica, separated by isocratic high-performance liquid chromatography, and quantitated by radioimmunoassay using a sensitive but suitably cross-reacting angiotensin II antiserum. For the C-terminal angiotensin II metabolites (2-8)heptapeptide, (3-8)hexapeptide, and (4-8)pentapeptide, overall recoveries of 10 fmol peptide added to 1 ml of plasma were (mean +/- SD), 74 +/- 6, 68 +/- 8, and 67 +/- 11%, respectively. The detection limit for these peptides in plasma was 0.2 fmol/ml. Blanks were below the detection limits. In eight seated normal subjects treated for 4 days with enalapril, 20 mg p.o., q.d., angiotensin II metabolites tended to decrease during the 4 postdrug hours. However, their cumulated concentration in relation to octapeptide increased from 54 to 163% on Day 1 and from 62 to 103% on Day 4. After 4 hours of converting enzyme inhibition with enalapril there was still a close correlation between plasma renin activity and angiotensin-(1-8)octapeptide level (r = 0.83, p less than 0.05) and between blood angiotensin I and angiotensin-(1-8)octapeptide levels (r = 0.86, p less than 0.01). Adding angiotensin I in vitro raised the angiotensin-(1-8)octapeptide levels after incubation at 4 degrees C for 4 hours. Thus, immunoreactive "angiotensin II" does not disappear after converting enzyme inhibition largely because of the cumulated contribution of cross-reacting metabolites and partly because of in vitro generation of true angiotensin II.

Adult↗
PubMed1986

Four-hour infusions of synthetic atrial natriuretic peptide in normal volunteers.

Two doses of synthetic atrial natriuretic peptide (0.5 and 5.0 micrograms/min) and its vehicle were infused intravenously for 4 hours in eight salt-loaded normal volunteers, and the effect on blood pressure, heart rate, renal hemodynamics, solute excretion, and secretion of vasoactive hormones was studied. The 0.5 micrograms/min infusion did not alter blood pressure or heart rate, whereas the 5.0 micrograms/min infusion significantly reduced the mean pressure by 20/9 mm Hg after 2.5 to 3 hours and increased the heart rate slightly. Inulin clearance was not significantly changed, but the mean p-aminohippurate clearance fell by 13 and 32% with the lower and higher doses, respectively. Urinary excretion of sodium and chloride increased slightly with the lower dose. With the higher dose, a marked increase in urinary excretion of sodium, chloride, and calcium was observed, reaching a peak during the second hour of the infusion. Potassium and phosphate excretion did not change significantly. A brisk increase in urine flow rate and fractional water excretion was seen only during the first hour of the high-dose infusion. Signs and symptoms of hypotension were observed in two subjects. No change in plasma renin activity, angiotensin II, or aldosterone was observed during either infusion, but a marked increase occurred after discontinuation of the high-dose infusion. In conclusion, the 5 micrograms/min infusion induced a transient diuretic effect, delayed maximal natriuretic activity, and a late fall in blood pressure, with no change in inulin clearance but a dose-related decrease in p-aminohippurate clearance. Despite large amounts of sodium excreted and blood pressure reduction, no counterregulatory changes were observed in the renin-angiotensin-aldosterone system or plasma vasopressin levels during the infusion.

Adult↗
PubMed1986

Haemodynamic role of vasopressin released during Finnish sauna.

The effect of vasopressin released during Finnish sauna on blood pressure, heart rate and skin blood flow was investigated in 12 healthy volunteers. Exposure to the hot air decrease body weight by 0.6 to 1.25 kg (mean = 0.8 kg, P less than 0.001). One hour after the end of the sauna sessions, plasma vasopressin was higher (1.7 +/- 0.2 pg/ml, P less than 0.01 mean +/- SEM) than before the sauna (1.0 +/- 0.1 pg/ml). No simultaneous change in plasma osmolality, plasma renin activity, plasma norepinephrine, epinephrine, cortisol, aldosterone, beta-endorphin and metenkephalin levels was observed. Despite the slight sauna-induced elevation in circulating vasopressin, intravenous injection of the specific vascular vasopressin antagonist d(CH2)5Tyr(Me)AVP (5 micrograms/kg) 1 h after the sauna had no effect on blood pressure, heart rate or skin blood flow. These data suggest that vasopressin released into the circulation during a sauna session reaches concentrations which are not high enough to interfere directly with vascular tone.

Adult↗
PubMed1986

Ambulatory blood pressure monitoring in adolescent untreated hypertensive patients.

Ambulatory blood pressure profiles were obtained with the portable semi-automatic blood pressure recorder Remler M2000 in groups of 20 adolescents, 20 young and 20 middle-aged adults and 20 elderly untreated patients, all considered by their physician to be hypertensive. It was found that adolescents who are hypertensive when seeing their physician are more often normotensive outside the physician's office than adult and elderly patients under similar conditions. The increased heart rate variability which was detected in adolescents was not associated with an enhanced blood pressure variability.

Adolescent↗
PubMed1986

Responsiveness of renin secretion: a key mechanism in the maintenance of blood pressure.

The renin-angiotensin system is known to respond to various stimuli with a marked increase in its activity. This phenomenon is well known in relationship to changes in sodium balance. Thus, the antihypertensive effect of diuretics is often blunted or even abolished by an excessive renin response. Water deprivation and alpha-adrenoceptor blockade also elicit considerable renin responses, which as a result become a predominant factor in blood pressure maintenance. Accordingly, the renin system plays a very important role in blood pressure regulation not just because it is spontaneously activated under steady-state conditions, but even more because of its responsiveness to pharmacological and other stimuli. This may explain the surprising efficacy of angiotensin converting enzyme inhibitors, which block the generation of angiotensin II, and thereby all vascular effects of spontaneously elevated renin levels as well as of any renin response.

Adrenergic alpha-Antagonists↗
PubMed1986

Clinical pharmacology of atrial natriuretic (3-28) eicosahexapeptide.

The clinical pharmacology of a synthetic rat atrial natriuretic peptide (rANP) was evaluated in normal volunteers. During a dose-ranging study at 1-40 micrograms/min we observed a dose-dependent decrease in mean intra-arterial blood pressure, an acceleration of the heart rate and a transient increase in blood flow to the skin. During a 4-h constant-dose infusion at 0.5 and 5.0 micrograms/min, inulin clearance remained unchanged but there was a dose-related fall in paraaminohippurate (PAH) clearance and an increase in the filtration fraction. Urinary excretion of sodium, chloride and calcium increased in a dose-related fashion, but with the high dose the excretion curve had a bell-shape. No change in plasma renin activity, angiotensin II and aldosterone was observed during the rANP infusion despite the excretion of large amounts of sodium and a blood pressure reduction with the high dose. Indocyanine green clearance, a measure of hepatic blood flow, was significantly decreased by a 2-h rANP infusion at 1.0 microgram/min. In normal volunteers, therefore, rANP induced vasodilation and blood pressure reduction, a decrease in renal and hepatic blood flow and a natriuretic and transient diuretic effect without activation of the renin-angiotensin-aldosterone system.

Animals↗
PubMed1986

[Absence of a role for the parasympathetic nervous system in the hemodynamic response to atriopeptin III in the normotensive rat].

The influence of the parasympathetic nervous system on the cardiovascular response to a synthetic atrial peptide (atriopeptin III) was examined in conscious normotensive rats utilizing the technique of radiolabelled microspheres. Atriopeptin III was infused intravenously for 30 min at a rate of 1 microgram/min in rats pretreated with a bolus intravenous injection of atropine, 150 micrograms (n = 8), or of its vehicle (n = 8). Additional animals (n = 9) received the vehicle of both atropine and atriopeptin III. The atrial peptide decreased mean blood pressure to similar extent in rats pretreated with atropine (from 124 +/- 4.5 to 108 +/- 5.3 mmHg, mean +/- SEM, p less than 0.05) and in the controls (from 123 +/- 3.8 to 105 +/- 3.8 mmHg, p less than 0.05). Heart rate rose significantly after administration of atropine. After the 30 minute infusion, cardiac index was significantly lower (p less than 0.05) in both groups infused with atriopeptin III (23.4 +/- 2.3 after atropine pretreatment and 25.1 +/- 2.2 ml/min X 100 g without atropine) than in the group of rats given only the vehicle of both atropine and atriopeptin III (32.4 +/- 2.8 ml/min X 100 g). There was no significant difference in regional blood flow distribution within the three groups of rats. These data therefore indicate that in conscious rats atriopeptin III reduces blood pressure and cardiac output without concomitantly modifying regional blood flow distribution. They also suggest that the parasympathetic nervous system does not contribute to the hemodynamic response to atriopeptin III.

Animals↗
PubMed1986

[Effect of synthetic atrial natriuretic factors on various regional blood flows in the healthy subject].

The effects of continuous infusions of 2 synthetic atrial natriuretic peptides Ile12-(3-28) (rANP) and Meth12-(3-28) (hANP) eicosahexapeptides on blood pressure, heart rate, skin blood flow, glomerular filtration rate, renal plasma flow, apparent hepatic blood flow, and carotid blood flow were evaluated in normal volunteers. A rANP infusion at increasing rates (1-40 micrograms/min) induced a decrease in blood pressure, an increase in heart rate and in skin blood flow linearly related to the dose administered. In contrast, hANP infusion at 1 microgram/min for 4 hours induced an initial increase followed by a secondary fall in skin blood flow without blood pressure changes. A 4-hour rANP infusion at 0.5 and 5 mcg/min did not alter glomerular filtration rate but induced a delayed and dose-related fall in renal plasma flow from 531 to 461 (p less than 0.05), and from 554 to 342 ml/min (p less than 0.001) respectively, with a consequential rise in the filtration fraction. The 5 mcg/min dose furthermore significantly reduced blood pressure following a latency period of 2.5 hours. A 2-hours rANP infusion at 0.5 micrograms/min induced a fall in apparent hepatic blood flow from 1,087 to 863 ml/min (p less than 0.01), without simultaneously altering blood pressure. Similarly, a 2-hour hANP infusion at 2 micrograms/min altered neither blood pressure nor carotid blood flow. In conclusion, ANP infusion induced changes in systemic and regional hemodynamics varying in direction, intensity and duration.

Atrial Natriuretic Factor↗
PubMed1986

Clinical pharmacology of the angiotensin converting enzyme inhibitor, enalapril.

Enalapril is a new angiotensin converting enzyme inhibitor which, when absorbed by the digestive tract, is converted to enalaprilat. This metabolite is, in fact, the active form of enalapril. Its duration of action is sufficiently long so that enalapril can be administered in a single daily dose. Enalapril has been proved to be a highly effective therapeutic agent which is well tolerated by patients with arterial hypertension or severe congestive heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

[What have we learned about inhibitors of the renin-angiotensin system?].

With orally active angiotensin converting inhibitors it is now possible to block the renin-angiotensin system chronically. These agents given alone normalize blood pressure of many hypertensive patients. In the remaining, an additional salt subtraction, induced for example by diuretics, is necessary to further reduce blood pressure. In patients with congestive heart failure, angiotensin converting enzyme inhibitors increase cardiac output and exercise capacity, both acutely and chronically. Adverse reactions resulting from blockade of the renin-angiotensin system can be predicted to a large extent and therefore are most often easily avoided. Angiotensin converting enzyme inhibitors like captopril and enalapril, because of their efficacy and good acceptability are likely to become important drugs for the treatment of hypertension and congestive heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

[Normalization of renin secretion by neuropeptide Y in adrenalectomized rats with glucocorticoid-induced hypertension].

In the periphery, neuropeptide Y is present in the circulation, in the adrenal medulla as well as at the level of nerve endings and of the juxtaglomerular apparatus. The aim of the present study was to assess the effect of this neuropeptide on renin secretion. Normotensive rats were biadrenalectomized or sham-operated and made hypertensive with methylprednisolone acetate (20 mg/kg s.c. once weekly). Deoxycorticosterone pivalate (10 mg/kg s.c. once weekly) was also given to prevent mineralocorticoid deficiency. Two weeks after that initial surgery 12 adrenalectomized rats and 8 sham-operated rats were infused for 30 min with neuropeptide Y (0.1 microgram/min) whereas 8 adrenalectomized rats and 9 sham-operated rats received in similar conditions the vehicle of neuropeptide Y (10 microliters/min). At that time, the rats were conscious and there was no significant difference in blood pressure and heart rate between the 4 groups of rats. At the end of the experiment, adrenalectomized rats exhibited a markedly stimulated renin-angiotensin system. Neuropeptide Y made it possible to normalize plasma renin activity in these rats, thus suggesting that neuropeptide Y plays an important role in regulating renin secretion.

Adrenalectomy↗
PubMed1986

Regulation of renin secretion in conscious adrenalectomized rats with glucocorticoid-induced hypertension.

The effect of adrenalectomy on renin secretion was investigated in conscious rats with glucocorticoid-induced hypertension. Adrenalectomized and sham-operated rats were made hypertensive with methylprednisolone acetate (20 mg/kg s.c. once/week X 2 weeks) supplemented with deoxycorticosterone pivalate (10 mg/kg s.c. once/week X 2 weeks). During the 2 week developmental phase of hypertension, tap water or isotonic saline was given as drinking fluid to respectively 10 and 13 adrenalectomized rats and 10 and 11 sham-operated rats. On the day of the acute administration of captopril or vehicle there was no significant difference in body weight, mean blood pressure, heart rate, serum electrolytes and plasma norepinephrine levels between the 4 groups of rats. Circulating epinephrine could not be detected in adrenalectomized rats. Plasma renin activity was markedly higher in adrenalectomized rats than in the sham-operated rats even after sodium supplementation. Captopril (10 mg/kg i.v.) produced no significant blood pressure lowering effect in rats given tap water to drink, either adrenalectomized (n = 11) or sham-operated (n = 10). These findings indicate that the activation of the renin-angiotensin system in adrenalectomized rats with glucocorticoid-induced hypertension is not directly mediated by the development of adrenal failure. They also show that the maintenance of high blood pressure in this form of experimental hypertension is not significantly enhanced when renin secretion is stimulated by adrenalectomy.

Adrenalectomy↗
PubMed1986

[Usefulness of ambulatory blood pressure monitoring in hypertensive patients].

Treated or untreated hypertensive patients may have very different blood pressure levels when measured by the doctor in his surgery and when measured by ambulatory monitoring during their usual everyday activities. It is now possible to record blood pressure non-invasively with a portable blood pressure measuring device, the Remler M2000. Using this device, we observed that less than half of the patients referred by their medical practitioner for hypertension had abnormally high blood pressures during their everyday activities. We also noted that the ambulatory blood pressure profile of a given hypertensive patient cannot be predicted from the blood pressure recorded by his or her doctor. Consequently, we concluded that ambulatory blood pressure recordings would appear to be essential for the detection of patients with high blood pressure readings at the doctor's surgery and during everyday activities. These patients probably include the only group which really needs appropriate antihypertensive therapy.

Ambulatory Care↗
PubMed1986

Blockade of the vascular effect of vasopressin in patients with mild essential hypertension.

The effect of circulating arginine vasopressin (AVP) on blood pressure, heart rate and skin blood flow was investigated in 8 untreated patients with mild essential hypertension using a specific antagonist of the pressor effect of AVP. Skin blood flow was measured with a laser Doppler flowmeter and blood pressure with a Remler M2000 recorder. The study was carried out in double-blind fashion using a cross-over design. Each patient received at a 60 min interval the AVP-antagonist, d(CH2)5Tyr(Me) AVP, 5 micrograms/kg i.v., and its vehicle. The sequence of treatment phases was randomly allocated. Pretreatment plasma AVP levels averaged 1.1 +/- 0.2 pg/ml (mean +/- SEM). Neither the AVP-antagonist nor its vehicle had any effect on blood pressure, heart rate and skin blood flow as well as on plasma renin activity and plasma catecholamines. It is therefore concluded that circulating AVP does not contribute to the maintenance of blood pressure in patients with mild essential hypertension and normal plasma AVP levels.

Adult↗
PubMed1985

[Hemodynamic effects of an inhibitor of the vascular effects of vasopressin in patients with congestive heart failure].

To assess the role of vasopressin (AVP) in congestive heart failure (CHF), we investigated 10 patients with CHF refractory to conventional treatment, before and 60 minutes after intravenous administration of 5 micrograms/kg of d(CH2)5Tyr(Me)AVP, a specific antagonist of AVP at the vascular receptor level. Heart rate, systemic arterial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac index by thermodilution, and cutaneous blood flow by laser-Doppler technique were measured. In 9 patients there was no significant hemodynamic and cutaneous blood flow response to the AVP antagonist. Plasma AVP was 2.3 +/- 0.8 pg/ml and plasma osmolality 284 +/- 14 mosm/kg H2O. The tenth patient had the most severe CHF. His plasma AVP was 55 pg/ml and plasma osmolality 290 mosm/kg. He responded to the AVP antagonist with a marked decrease in systemic arterial pressure from 115/61 to 79/41 mm Hg, in pulmonary arterial pressure from 58/31 to 33/13 mm Hg and in pulmonary capillary wedge pressure from 28 to 15 mm Hg. Simultaneously cardiac index increased from 1.1 to 2.21 X min-1 X m-2 and cutaneous blood flow rose 5-fold. Thus, most patients with CHF have only moderately elevated plasma AVP and its role in determining peripheral vascular resistance appears to be limited. AVP may become important in rare patients presenting with marked hemodynamic instability and very high plasma AVP.

Adult↗
PubMed1985

[Usefulness of ambulatory registration of arterial pressure in therapeutic trials of antihypertensive agents].

In the context of a controlled antihypertensive drug trial, blood pressure readings obtained by the physician in his office were compared with ambulatory blood pressures recorded with the semi-automatic Remler device. The beta-adrenoceptor blocking agent timolol or methyldopa were administered in double-blind fashion to 30 patients with uncomplicated essential hypertension. All exhibited a diastolic office blood pressure of greater than 95 mm Hg at the end of a 4-week placebo period. All patients then received a combination of hydrochlorothiazide (25 mg/d) and amiloride (2.5 mg/d). After 4 weeks of diuretic therapy, timolol (10 mg/d, n = 14) or methyldopa (250 mg/d, n = 16) were added randomly for 6 weeks. The dose of all antihypertensive agents was doubled after 2 weeks of therapy with diuretics combined with timolol (n = 7) or methyldopa (n = 16) because of the persistence of diastolic blood pressure levels of greater than 90 mm Hg at the office. When assessed in the office, the antihypertensive effect of timolol and methyldopa was similar. During ambulatory blood pressure monitoring, however, pressure levels tended to be lower in the patients given timolol (p less than 0.05 for the diastolic). These data show that ambulatory blood pressure monitoring may be very useful in comparing the antihypertensive efficacy of different drugs.

Adult↗