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Biomedical subjects

J Biollaz

Publications and source records attributed to J Biollaz.

At least 127 records · Page 7Linked to original sources
PubMed1986

Enprostil, in contrast to cimetidine, does not inhibit propranolol metabolism.

Enprostil, an orally active prostaglandin E2 analog, is undergoing clinical trials in the treatment of peptic ulcer disease. Because results of animal studies suggested that prostaglandins might affect both hepatic drug metabolizing ability and hepatic blood flow, the effects of enprostil on drug elimination were studied and compared with those of the standard antiulcer drug cimetidine in a double-blind, randomized, crossover study of nine normal subjects. Cimetidine reduced the oral clearance of propranolol by 50%, consistent with the inhibition of drug metabolism reported in previous studies. On the other hand, enprostil had no effect on propranolol elimination. Neither drug altered liver blood flow as assessed either by the clearance of indocyanine green or by the technique of dual route of administration of propranolol. Thus in contrast to cimetidine, enprostil had no effect on hepatic drug metabolism.

Administration, Oral↗
PubMed1986

Chronic treatment of hypertensive patients with converting enzyme inhibitors.

It is widely accepted that pharmacologic reduction of the blood pressure of hypertensive patients reduces the risk of at least some of the major cardiovascular complications (1-5). All major studies were carried out before orally active converting enzyme inhibitors had become available. In other words, very effective antihypertensive drugs have been around for quite some time and have already proven their efficacy. Therefore, the considerable enthusiasm that has developed during the very recent years for the new converting enzyme inhibitors should be evaluated in the light of previously available antihypertensive drugs, the more so, as drugs cheaper than converting enzyme inhibiting agents are presently available. Thus, the increased expense when using this new class of antihypertensive compounds should be justified by a therapeutic gain. When evaluating a class of antihypertensive drugs such as converting enzyme inhibitors, there are basically three main considerations: What is their efficacy in long-term use? This includes the effect on blood pressure, on heart, on hemodynamics, and on blood flow distribution. What are the metabolic effects? What is the effect on sodium and potassium excretion? How are the serum lipids affected by its use? Are there any untoward effects related either to the chemical structure of the compound per se or rather to the approach? In particular, are there any central effects of the drug which can cause discomfort to the patient? The following discussion has the principal aim to review these aspects with chronic use of oral converting enzyme inhibiting agents without, however, even attempting to provide an exhaustive review of the subject.

Angiotensin I↗
PubMed1986

Hormonal, global, and regional haemodynamic responses to a vascular antagonist of vasopressin in patients with congestive heart failure with and without hyponatraemia.

The pathophysiological role of an increase in circulating vasopressin in sustaining global and regional vasoconstriction in patients with congestive heart failure has not been established, particularly in patients with hyponatraemia. To assess this further, 20 patients with congestive heart failure refractory to digoxin and diuretics were studied before and 60 minutes after the intravenous injection (5 micrograms/kg) of the vascular antagonist of vasopressin [1(beta-mercapto-beta,beta-cyclopentamethylene-propionic acid), 2-(0-methyl) tyrosine] arginine vasopressin. Ten patients were hyponatraemic (plasma sodium less than 135 mmol/l) and 10 were normonatraemic. In both groups of patients the vascular vasopressin antagonist did not alter systemic or pulmonary artery pressures, right atrial pressure, pulmonary capillary wedge pressure, cardiac index, or vascular resistances. Furthermore, there was no change in skin and hepatic blood flow in either group after the injection of the vascular antagonist. Only one patient in the hyponatraemic group showed considerable haemodynamic improvement. He had severe congestive heart failure and a high concentration of plasma vasopressin (51 pmol/l). Plasma renin activity, vasopressin, or catecholamine concentrations were not significantly changed in response to the administration of the vasopressin antagonist in either the hyponatraemic or the normonatraemic groups. Patients with hyponatraemia, however, had higher baseline plasma catecholamine concentrations, heart rate, pulmonary pressure and resistance, and lower hepatic blood flow than patients without hyponatraemia. Plasma vasopressin and plasma renin activity were slightly, though not significantly, higher in the hyponatraemic group. Thus the role of vasopressin in sustaining regional or global vasoconstriction seems limited in patients with congestive heart failure whether or not concomitant hyponatraemia is present. Vasopressin significantly increases the vascular tone only in rare patients with severe congestive heart failure and considerably increased vasopressin concentrations. Patients with hyponatraemia do, however, have raised baseline catecholamine concentrations, heart rate, pulmonary arterial pressure and resistance, and decreased hepatic blood flow.

Adult↗
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

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

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

[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↗
PubMed1985

Cimetidine inhibition of ethmozine metabolism.

Ethmozine, a phenothiazine antiarrhythmic, is effective in atrial and ventricular arrhythmias. Because of the extensive hepatic metabolism of ethmozine, we investigated the effects of the potent hepatic enzyme inhibitor cimetidine on the kinetics and dynamics of ethmozine. Eight healthy men 22 to 40 years old (means = 27.6 years) received a single, oral, 500 mg dose of ethmozine. Ethmozine dosing was repeated 15 days later after cimetidine, 300 mg four times a day for 7 days. Plasma samples were drawn over the next 24 hours for measurement of ethmozine. ECGs were obtained 1, 2, 4, 8, and 24 hours after each dose. After cimetidine, ethmozine clearance fell from 38.2 +/- 10.7 to 19.7 +/- 4.2 ml/kg/min and the t1/2 increased from 3.3 +/- 1.3 to 4.6 +/- 1.6 hours. Ethmozine prolonged the PR and QRS intervals, but there was no detectable further increase after cimetidine. Heart rate and blood pressure were not altered by ethmozine either alone or in the combination. We conclude that cimetidine increases plasma concentrations of ethmozine but did not induce any detectable further increase in the PR or QRS intervals.

Adult↗
PubMed1985

Sodium chloride-induced partial inhibition in vivo of alpha 2-adrenoceptor agonist function.

Recent research has demonstrated that sodium diminishes the affinity of alpha 2-adrenoceptors for agonists in vitro. Clonidine, a highly specific agonist for alpha 2-receptors, has a transient hypertensive effect when administered parenterally. We studied in conscious anephric Wistar rats the effect of equimolar saline or mannitol solutions on the hypertensive response to clonidine administered subcutaneously in doses of 10, 100 and 1000 micrograms/kg body weight. Prior saline infusion reduced the hypertensive response to the two higher doses of clonidine by 65 and 70%, and displaced the slope of the dose-response curve downwards, but mannitol had no such effect. Pre-treatment with the alpha 2-antagonist yohimbine abolished the differences in clonidine-induced pressor response between saline-treated, mannitol-treated and control rats. On the contrary, after pre-treatment with the alpha 1-antagonist prazosin, the pressor action of clonidine was significantly reduced in the saline-infused rats compared to the other two groups. Thus the saline-induced blunting of the pressor response elicited by clonidine could be negated by prior alpha 2- but not alpha 1-blockade, indicating that sodium interfered with the stimulation of post-synaptic vascular alpha 2-adrenoceptors. These findings indicate that loading with sodium chloride attenuates the alpha 2-adrenoceptor function in vivo. Based on this, we suggest that the mechanism by which sodium excess causes a rise in blood pressure involves modification of the alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1984

Acute cardiovascular effects of two central phenylethanolamine-N-methyl-transferase inhibitors in unanesthetized desoxycorticosterone-salt hypertensive rats.

SKF 64139, an inhibitor of phenylethanolamine-N-methyltransferase (PNMT), has a marked hypotensive effect in models of sodium-dependent hypertension. The mechanism of this effect is obscure, the compound having in addition alpha-adrenoceptor blocking properties. We compared the acute effects of SKF 64139 with those of LY 134046, another PNMT inhibitor with minimal alpha-blocking capacity, in desoxycorticosterone-salt hypertensive rats. The former agent produced profound hypotension whereas the latter caused only bradycardia. Both induced a similar pronounced suppression of PNMT activity in the C1 and C2 region of the medulla oblongata. These results suggest that the alpha-adrenergic effect rather than PNMT inhibition accounts for the acute lowering of blood pressure in this model.

Animals↗
PubMed1984

Ambulatory blood pressure recording to identify hypertensive patients who truly need therapy.

Ambulatory blood pressure profiles were obtained with the Remler system, a portable semi-automatic blood pressure recorder, in 245 untreated patients considered by their physician to be hypertensive. The average blood pressures recorded during the usual daily activities of the patients were greater than 140 mmHg for the systolic and greater than 89 mmHg for the diastolic in only 96 (39%) and 107 (44%) of them respectively. Blood pressure monitoring in ambulatory patients appears to be useful for the practitioner to detect those patients who require antihypertensive therapy. Possibly, unnecessary therapy of only seemingly hypertensive patients may be avoided by this technique.

Adolescent↗
PubMed1983

[Treatment of hypertensive crisis with captopril].

The usefulness of captopril in managing hypertensive emergencies was evaluated in 9 untreated patients. During the 30 minutes following oral administration of 25 mg of this angiotensin converting enzyme inhibitor, blood pressure decreased from 239/134 to 204/118 mm Hg (p less than 0.05). At that time, furosemide (20 mg i.v. or 40 mg orally) had to be added in 5 patients to further decrease pressure levels. Ninety to 120 minutes after starting therapy, an additional dose of captopril (100 mg orally) was given to all patients. 12 and 24 hours after admission respectively, blood pressure averaged 140/93 and 139/86 mm Hg in the patients treated with captopril alone and 166/107 and 153/91 mm Hg in those treated with both captopril and furosemide. The blood pressure fall was well tolerated and no adverse effect was induced by captopril. These results show that captopril given alone or in association with a diuretic makes it possible to deal quickly and effectively with hypertensive crises without necessarily requiring monitoring in an intensive care unit.

Administration, Oral↗
PubMed1983

[Profiles and variations of ambulatory arterial pressure in treated and untreated hypertensive patients].

It is now possible to record numerous ambulatory blood pressures by a noninvasive method using the Remler, a portable semi-automatic device. The blood pressure profiles obtained with this recorder in hypertensive patients during customary daily activities have revealed the existence of a circadian blood pressure variation. Thus, blood pressure is highest in the morning, lowest early in the afternoon and tends to increase again late in the afternoon. This circadian variation is not modified by treatment with diuretics and/or betablockers. These blood pressure recordings also made it possible to establish that antihypertensive therapy with these agents does not modify blood pressure variability over the day.

Adrenergic beta-Antagonists↗
PubMed1983

Hypertensive crisis treated with orally administered captopril.

The value of the orally active converting enzyme inhibitor captopril in managing hypertensive crisis was tested in 9 untreated patients admitted to the emergency room, who were in need of rapid blood pressure reduction because of signs and symptoms of neurological and/or cardiac complications. During the 30 min following administration of captopril 25 mg the blood pressure decreased from 239/134 +/- 12/4 mmHg (mean +/- SEM) to 204/118 +/- 8/4 mmHg (p less than 0.05). From that time on, captopril 200 to 300 mg/day was continued for 2 to 5 days. In 5 patients furosemide in a total dose of 40 to 160 mg i.v. or p.o. had also to be given in order to control the blood pressure. 12 and 24 h after admission blood pressure averaged 140/93 and 139/86 mmHg respectively, in the patients treated with captopril alone, and 166/107 and 153/91 mmHg in those treated both with captopril and furosemide. The pronounced fall in blood pressure produced by blockade of the renin system was well tolerated and did not cause tachycardia. It appears, therefore, that captopril given alone or in association with a diuretic makes it possible to treat the hypertensive crisis without the need for monitoring in an intensive care unit.

Administration, Oral↗
PubMed1983

Blood pressure maintenance in awake dehydrated rats: renin, vasopressin, and sympathetic activity.

The role of vasopressin, the renin system, and sympathetic activity in sustaining blood pressure in the dehydrated state was investigated in normotensive nonanesthetized male Wistar rats. After 48-h dehydration, plasma arginine vasopressin was 14.0 +/- 1.7 pg/ml and plasma norepinephrine 0.46 +/- 0.05 ng/ml. In another group of rats in which the angiotensin converting enzyme inhibitor (MK 421, 5 mg po twice daily) was administered throughout the dehydration period, blood pressure was reduced by more than 20% (P less than 0.001), and both plasma arginine vasopressin and norepinephrine were higher at 23.4 +/- 3.9 pg/ml (P less than 0.01) and 0.83 +/- 0.07 ng/ml (P less than 0.01), respectively. Taken together, in rats with or without converting enzyme blockade, there was an inverse correlation between mean blood pressure and plasma arginine vasopressin (r = 0.67, P less than 0.01) as well as plasma norepinephrine (r = 0.82, P less than 0.01) levels. The acute administration of a specific vasopressin pressor inhibitor (dPVDAVP) reduced mean blood pressure in the rats with a blocked renin system by 16.9 mmHg (P less than 0.001). In rats without converting enzyme inhibition, the induced fall was only 6.4 mmHg. These results indicate that following 48-h dehydration the renin angiotensin system interacts with the vasopressin secretory mechanism to sustain blood pressure, with renin playing a predominant role. They further suggest that, following blockade of the renin system, activation of the sympathetic nervous system probably also contributes to blood pressure maintenance.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1983

The clinical application of converting enzyme inhibitors.

Chronic blockade of the renin angiotensin system became possible when orally active inhibitors of angiotensin converting enzyme, the enzyme which catalyzes the transformation of angiotensin I into angiotensin II, were synthetized. Two compounds, captopril and enalapril, have been investigated in clinical studies. The decrease of the pressor response to exogenous angiotensin I and of the circulating levels of angiotensin II following administration of these inhibitors has been demonstrated to be directly related to the degree of suppression of plasma angiotensin converting enzyme activity. These inhibitors have been shown to normalize blood pressure alone in some hypertensive patients whereas in many others, satisfactory blood pressure control can be achieved only after the addition of a diuretic. Captopril and enalapril also markedly improve cardiac function of patients with chronic congestive heart failure. Chronic blockade of the renin angiotensin system has therefore provided an interesting new approach to the treatment of clinical hypertension and heart failure.

Angiotensin-Converting Enzyme Inhibitors↗