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Biomedical subjects

B Waeber

Publications and source records attributed to B Waeber.

At least 343 records · Page 19Linked to original sources
PubMed1985

Acute hemodynamic effect of a vascular antagonist of vasopressin in patients with congestive heart failure.

To assess the role of arginine vasopressin (AVP) in congestive heart failure (CHF), 10 patients with CHF refractory to conventional treatment were studied 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 with no significant hemodynamic and cutaneous blood flow response to the AVP antagonist, baseline values (mean +/- standard deviation) were: heart rate, 77 +/- 14 beats/min; systemic arterial pressure, 120/79 +/- 18/8 mm Hg; pulmonary arterial pressure, 42/21 +/- 12/8 mm Hg; pulmonary capillary wedge pressure, 19 +/- 7 mm Hg; cardiac index, 2.2 +/- 0.6 liters/min/m2; plasma AVP, 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 level was 55 pg/ml and plasma osmolality was 290 mosm/kg. He responded to the AVP antagonist with a 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 2.2 liters/min/m2 and heart rate from 113 to 120 beats/min; cutaneous blood flow increased 5-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Transdermal clonidine therapy in hypertensive patients. Effects on office and ambulatory recorded blood pressure values.

The antihypertensive effect of clonidine hydrochloride delivered at a constant rate for seven days by transdermal disks was evaluated in seven patients with essential hypertension. Blood pressure values measured at the physician's office were not significantly decreased by one month of treatment with one (n = 2) or two (n = 5) once-weekly applied clonidine transdermal disks. In contrast, blood pressure values recorded during patients' customary daily activities by means of a portable blood pressure recorder were considerably reduced, from 159/97 +/- 2/2 to 136/76 +/- 7/5 mm Hg. Plasma drug concentration at the end of the fourth week averaged 1.22 +/- 0.24 ng/mL. Plasma renin, vasopressin, and epinephrine levels were not modified by clonidine, whereas plasma norepinephrine level was significantly reduced. Local skin erythema developed in three patients and dry mouth in six. These findings suggest that clonidine transdermal disks lower blood pressure in hypertensive patients, but produce local skin lesions and general side effects.

Administration, Topical↗
PubMed1985

Haemodynamic and pharmacological effects of the converting enzyme inhibitor CGS 14824A in normal volunteers.

The converting enzyme inhibitor CGS 14824A was evaluated in 15 healthy male volunteers. First, the efficacy of a single 5 or 10 mg oral dose in antagonizing the pressor response to exogenous angiotensin I was tested in 2 subjects. Blood pressure and heart rate were monitored continuously through an intra-arterial catheter. CGS 14824A 5 mg reduced the response to angiotensin I within 75 min to 50%, and 10 mg within 1 h to less than 25%, and for a period of more than 4 h. Subsequently, plasma renin and converting enzyme activity, plasma angiotensin I, angiotensin II and aldosterone were measured serially before and up to 72 h following oral administration of 2, 5, 10 or 20 mg CGS 14824A to groups of 5 volunteers. Plasma converting enzyme activity fell to well below 10% of baseline within 1 h after administration of 5 mg or more CGS 14824A. Within 2 h following 2 mg p.o., a similarly low level was reached. Twenty four hours following the 20 mg dose, plasma converting enzyme activity was still below 10%. As expected, plasma renin activity and angiotensin I rose while angiotensin II and aldosterone fell following the 2 mg dose. This pattern of effects was enhanced by increasing the dose. Nonetheless, 24 h after the 20 mg dose, plasma angiotensin II and aldosterone had returned to their baseline levels. No side-effects occurred. Thus, in normal volunteers, CGS 14824A was an effective, potent and long acting converting enzyme inhibitor.

Adult↗
PubMed1985

The effect of the converting enzyme inhibitor HOE 498 on the renin angiotensin system of normal volunteers.

The converting enzyme inhibitor HOE 498 was evaluated in 12 normotensive male volunteers aged 21 to 26. The efficacy of single 5, 10 or 20 mg oral doses in blocking the pressor response to exogenous angiotensin I was tested in 3 of the subjects. All 3 doses of HOE 498 reduced the pressor response to exogenous angiotensin I to below 50% of control within 1,5 h following administration of the drug. Plasma renin and converting enzyme activity, blood angiotensin I, as well as plasma angiotensin II and aldosterone were measured serially before and up to 72 h following oral administration of a single dose of 2.5, 5, 10 or 20 mg of HOE 498 to groups of 5 volunteers each. As expected, blood angiotensin I levels and plasma renin activity rose while plasma converting enzyme activity, plasma angiotensin II and aldosterone concentration fell after administration of the drug. While the dose of 2.5 mg did not reduce plasma converting enzyme activity below 20% of control, the higher doses all resulted in plasma converting enzyme inhibition exceeding 90%. No side-effects were observed. It is concluded that in normal volunteers HOE 498 is an effective potent and long-acting converting enzyme inhibitor. Based on these preliminary findings it is expected that 5 mg HOE 948 will turn out to be adequate for therapeutic use.

Administration, Oral↗
PubMed1985

Cardiac mass in glucocorticoid-hypertensive rats with and without circulating adrenaline.

There is evidence that catecholamines may promote the development of cardiac hypertrophy in hypertension. To test the hypothesis that adrenaline directly determines left ventricular mass, normotensive Wistar rats were made adrenaline-deficient by adrenalectomy and hypertensive by administration of glucocorticoid. Blood pressure, heart rate, and body weight of the adrenalectomised group were not significantly different from a glucocorticoid treated control group with intact adrenals. Heart weight was significantly lower in the adrenalectomised rats, but this difference disappeared when heart weight was adjusted for body weight. It appears therefore that the presence or absence of adrenaline does not significantly affect cardiac mass in the presence of hypertension in this animal model.

Adrenalectomy↗
PubMed1985

Blood pressure response to antihypertensive therapy: ambulatory versus office blood pressure readings.

Blood pressure readings obtained by the physician in his office and ambulatory blood pressures recorded with the semi-automatic Remler device, were compared during a controlled antihypertensive drug trial. Either timolol or methyldopa was administered in in double-blind fashion to 30 patients with uncomplicated essential hypertension. All exhibited a diastolic office blood pressure greater than 95 mmHg at the end of a four-week placebo period. All patients then received a combination of hydrochlorothiazide (25 mg/day) and amiloride (2.5 mg/day). After four weeks of diuretic therapy, timolol (10 mg/day, n = 14) or methyldopa (250 mg/day, n = 16) were added randomly for six weeks. The dose of all antihypertensive agents was doubled after two weeks of therapy with diuretics combined with timolol (n = 7) or methyldopa (n = 16) because of the persistence of diastolic blood pressure levels greater than 90 mmHg 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 were lower in the patients given timolol (P less than 0.05 for the diastolic). With both regimens, the blood pressure response measured outside the clinic during usual daily activities could not be predicted from that observed with office blood pressure readings. Furthermore the magnitude of the drug induced blood pressure decrease was more reproducible in time when determined outside the clinic. These data suggest that ambulatory blood pressure monitoring is more precise in evaluating the efficacy of antihypertensive therapy than office blood pressure measurement.

Activities of Daily Living↗
PubMed1985

The present molecules of converting enzyme inhibitors.

Since the end of 1976 ten orally active converting enzyme inhibitors [SQ 14,225 (captopril), MK 421 (enalapril), MK 422, MK 521 (lysinopril), RHC 3659, CGS 13945, CGS 13928C, CGS 14824A, Hoe 498, S 9490-3, and Ro 31-2848] have been evaluated by our group in normal volunteers. Their ability to blunt the pressor response to exogenous angiotensin I and their effect on the different components of the renin-angiotensin system were tested. This approach has made it possible to establish the efficacy of the different molecules and to predict with a considerable degree of accuracy onset and duration of action of the various compounds as well as the doses needed to treat hypertensive patients. All ten molecules were effective in blocking converting enzyme and thereby the pressor response to angiotensin I. Potency and time course of the inhibition varied considerably among the compounds. Thus, a number of highly effective angiotensin-converting enzyme inhibitors are actually in clinical evaluation and several of them should become available for general clinical use within a few years.

Angiotensin II↗
PubMed1985

Effects of angiotensin converting enzyme inhibition: a clinical point of view.

Angiotensin converting enzyme inhibitors were developed to prevent the in vivo generation of angiotensin II and thereby to reduce peripheral vasoconstriction. However, these compounds exert some additional effects that may or may not be angiotensin dependent. These include potential sodium diuresis, bradykinin accumulation, prostaglandin release, blunting of sympathetic activity, parasympathomimetic actions, central effects, redistribution of blood flow toward some particularly important organs. Only the comprehensive assessment of the many complex interactions that exist between the renin-angiotensin and several other regulatory systems reveals the complete therapeutic profile of this class of pharmacologic agents.

Angiotensin I↗
PubMed1985

Angiotensin II, vasopressin, and sympathetic activity in conscious rats with endotoxemia.

The role of the sympathetic nervous system, angiotensin II (ANG II), and arginine vasopressin (AVP) in maintaining blood pressure (BP) during endotoxic shock was investigated in 117 conscious male Wistar rats. After intravenous injection of 2 mg Escherichia coli endotoxin, mean BP fell within 5 min by approximately 50 mmHg and rose again to approach base-line levels within 90 min. At that time, plasma renin activity, plasma norepinephrine (NE), and vasopressin levels of the endotoxin-treated animals were, respectively, 12-, 10-, and 54-fold (P less than 0.001) higher than those of the controls. The BP effect of either prazosin (0.125 mg iv), captopril (2.5 mg iv), or d(CH2)5Tyr(Me)AVP (5 micrograms iv), a specific antagonist of the vascular effect of AVP, was evaluated over a 30-min observation period starting 90 min after administration of endotoxin or its vehicle. Captopril reduced mean BP from 116 +/- 1.8 to a low of 109 +/- 2.1 (SE) mmHg (P less than 0.05, n = 8) only in rats pretreated with endotoxin, whereas the vasopressin antagonist had no depressor effect even during endotoxemia. The BP drop induced by prazosin in rats exposed to endotoxin (-21 +/- 3.3 mmHg, n = 6) did not significantly differ from that observed in control rats (-14 +/- 3.4 mmHg, n = 6). A dose-response curve to NE, ANG II, and lysine vasopressin was also performed. In endotoxin-treated rats the mean BP response to all agonists was markedly suppressed (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1985

Salt subtraction in patients on maintenance hemodialysis. Efficacy and limitations.

In 6 hypertensive patients with terminal renal failure maintained on hemodialysis, the effects of 'salt subtraction' and of sequential ultrafiltrating were evaluated. Following each of 3 weekly hemodialysis sessions, salt subtraction was carried out by ultrafiltrating 1 liter and simultaneously infusing an equal volume of 5% dextrose. This resulted in a net sodium loss without hypovolemia. After a 2-week period of this procedure, the blood pressure prior to dialysis was lower (156/76 +/- 12/5 mm Hg) than after a comparable number of sequential ultrafiltration sessions (181/88 +/- 10/6 mm Hg; mean +/- SEM). This difference was not statistically significant. At the same time, body weight was comparable at 64.4 +/- 3 and 64.7 +/- 4 kg, respectively. Neither plasma renin activity nor plasma catecholamines responded with a clear increase to either procedure. The limited effect on blood pressure and the renin system of a marked sodium removal during salt subtraction suggests that sodium must still be present in excess in these patients. The procedure of salt subtraction appears safe and subjectively well tolerated, but it can probably not be used as the sole means of decreasing total body sodium without associating dietary measures to reduce sodium intake.

Adult↗
PubMed1985

Shortcomings of office blood pressures in assessing antihypertensive therapy.

The antihypertensive effect of different agents was investigated in patients with essential hypertension both at the clinic and in the ambulatory state using the semi-automatic Remler M2000 blood pressure recorder. In 7 patients treated for 4 weeks with a transdermal therapeutic system delivering clonidine, blood pressures measured at the physician's office were not significantly decreased whereas blood pressures recorded during patients' customary daily activities were markedly reduced. In an additional study performed in double-blind fashion, the blood pressure lowering effect of timolol (10-20 mg/d, n = 14) and of methyldopa (250-500 mg/d, n = 16) were compared. These agents were given for 6 weeks in association with a baseline diuretic therapy of hydrochlorothiazide and amiloride. When assessed at the clinic, the antihypertensive effect of timolol and methyldopa was similar. During ambulatory blood pressure monitoring, however, pressure levels were lower (p less than 0.05 for the diastolic) in the patients given timolol. These data indicate that blood pressure monitoring outside the clinic makes it possible to detect important differences in the response to antihypertensive therapy even though, based on office blood pressure readings, no significant change occurs. It appears therefore desirable to include ambulatory blood pressure recordings in the design of drug trials.

Antihypertensive Agents↗
PubMed1985

Enhanced renin secretion in adrenalectomized rats with glucocorticoid-induced hypertension.

The role of circulating epinephrine in the regulation of renin release was studied in unanesthetized rats with glucocorticoid-induced hypertension. Biadrenalectomized Wistar rats were made hypertensive with methylprednisolone (20 mg/kg s.c. weekly) for 2 weeks and supplemented with deoxycorticosterone pivalate (10 mg/kg s.c. weekly). Sham-operated controls received the same treatment. Baseline weight, mean intra-arterial blood pressure and heart rate of the groups were the same. In both adrenalectomized and sham-operated rats plasma renin activity was determined after a 30 min infusion of the beta-adrenoceptor stimulant isoproterenol (40 ng/min) or its vehicle. Isoproterenol had no blood pressure effect and accelerated heart rate to a similar extent in rats with and without adrenals. Plasma renin activity was significantly higher in epinephrine-deficient than in sham-operated rats. Renin secretion was significantly enhanced by isoproterenol in both groups of rats. These data therefore indicate that in rats with glucocorticoid-induced hypertension the renin-angiotensin system is activated by adrenalectomy, despite the fact that adrenal insufficiency cannot develop. It also appears that rats lacking of circulating epinephrine for a prolonged period do not exhibit an abnormal responsiveness of renin secretion to the stimulation of renal beta-adrenoceptors.

Adrenalectomy↗
PubMed1985

Double-blind comparison of indapamide with a placebo in hypertensive patients treated by practicing physicians.

The antihypertensive effect of indapamide (2.5 mg/day) was compared to that obtained with a placebo in a controlled trial carried out by 11 physicians in their private practice. Thirty-one patients with uncomplicated essential hypertension were included. After a run-in period of 3 weeks without any treatment, either indapamide (n = 16) or a placebo (n = 15) were administered for 8 weeks in double-blind fashion. Blood pressure decreased in both groups. In patients treated with indapamide, systolic pressure was significantly lower than in those given the placebo at 3 out of the 4 follow-up visits; diastolic pressure, however, was significantly lower only at the end of the trial. Both the active drug and the placebo were well tolerated. No significant change in body weight, plasma potassium and uric acid occurred during the study in either group of patients. It appears therefore that indapamide, at a dose which apparently has no major diuretic effect, may be useful for practitioners in managing patients with mild to moderate hypertension.

Adult↗
PubMed1985

Plasma angiotensins under sustained converting enzyme inhibition with enalapril in normal humans.

During converting enzyme inhibition, a striking difference is found between plasma immunoreactive angiotensin (ANG) II and ANG-(1-8)octapeptide as specifically measured after high performance liquid chromatography (HPLC). The relative contributions to this difference of cross-reacting ANG I and shorter ANG peptides other than (1-8)octapeptide are not known. Eight normal volunteers were given a daily single oral dose of enalapril (20 mg) for 4 days. Plasma levels of ANG-(1-8)octapeptide, (2-8)heptapeptide, (3-8)hexapeptide and (4-8)pentapeptide as well as blood concentrations of ANG I and plasma angiotensin converting enzyme activity were measured before and 4 h post drug on the first and the last day of treatment. Plasma peptides were extracted with bonded-phase silica and separated by isocratic reversed-phase HPLC before radio-immunoassay. Significant cross-reactivity of an antiserum permitted the individual measurement of different ANG peptides and metabolites in plasma. During converting enzyme inhibition, the plasma levels of ANG metabolites tended to decrease, but they remained measurable. Thus, depending on the specificity of the antiserum used, conventional measurement of immunoreactive ANG II underestimates to various degrees the inhibition of angiotensin converting enzyme.

Adult↗
PubMed1985

Response of plasma vasopressin to changes in extracellular volume and/or plasma osmolality in patients on maintenance hemodialysis.

The effect of changes in extracellular volume versus changes in plasma osmolality on arginine vasopressin (AVP) release was studied in 6 patients with terminal renal failure maintained on chronic hemodialysis. The day of the study, the patients were treated by sequential ultrafiltration lasting 1 hour followed by a 3-hour conventional hemodialysis session. The ultrafiltration resulted in the removal of 460 to 1,170 ml (mean = 860 ml) of volume. Body weight during the combined procedures fell by 1.6 +/- 0.4 kg (mean +/- s.e.m.) while mean arterial pressure decreased only slightly. Plasma osmolality was unaffected by sequential ultrafiltration, but decreased from 313 +/- 4 mosm/kg H2O to 291 +/- 4 mosm/kg H2O during hemodialysis. Initial plasma AVP concentration was high at 4.45 +/- 0.25 pg/ml and remained unchanged during the sequential ultrafiltration at 4.55 +/- 0.37 pg/ml, but it fell during the hemodialysis to 2.47 +/- 0.45 pg/ml. A hypotensive episode observed in one patient towards the end of hemodialysis resulted in a sharp increase in plasma AVP concentration from 5.5 to 18 pg/ml. During the combined procedures, plasma AVP and plasma osmolality showed a close and linear correlation (r = 0.63, n = 23, p less than 0.001). These findings suggest that in patients on maintenance hemodialysis, changes in plasma osmolality play a predominant role in determining AVP secretion whereas a marked decrease in volume without ensuing hypotension has no effect on AVP release.

Blood Pressure↗