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Biomedical subjects

B Waeber

Publications and source records attributed to B Waeber.

At least 415 records · Page 23Linked to original sources
PubMed1979

Oral angiotensin-converting enzyme inhibitor in long-term treatment of hypertensive patients.

The antihypertensive effect of the orally active angiotensin-converting enzyme inhibitor captopril (SQ 14225) was assessed in 22 hypertensive patients of whom 17 were followed for periods ranging from 1 to 7 months. Of these, eight had essential hypertension, eight had renovascular hypertension, and six had hypertension associated with chronic renal failure. Blood pressure decreased markedly in all patients, including those with low renin levels. Nevertheless, the magnitude of blood pressure reduction correlated with the base-line plasma renin activity (r = 0.58, P less than 0.01). Increasing the dose of captopril from 25 to 200 mg did not enhance the amplitude of the antihypertensive effect but did increase its duration. Patients' blood pressure remained well controlled and free of side-effects with a maximal daily dose of up to 200 mg by mouth twice daily. Despite the blood pressure reduction, sodium excretion tended to increase, probably because of reduced aldosterone secretion. There was no evidence of orthostatic hypotension, and no escape from the antihypertensive effect was observed. These results indicate that chronic inhibition of the angiotensin-converting enzyme with an orally active compound offers a new, efficient, and well-tolerated approach to the treatment of hypertension.

Adult↗
PubMed1979

Captopril and salt subtraction to treat "uncontrollable" hypertension in haemodialysis patients.

Eight patients on chronic haemodialysis for six months to 7 years with hypertension resistant to ultrafiltration and antihypertensive therapy, received Captopril (SQ 14, 225) an orally active inhibitor of converting enzyme. With this therapy, blood pressure was controlled in the 4 patients with the highest plasma renin activity. In the other 4, this treatment had to be supplemented with "isovolumetric salt subtraction", i.e. following conventional dialysis, 1-2 litres of ultrafiltrate were replaced by an equal volume of 5% glucose. The slight hyponatraemia induced by this procedure (plasma sodium 128mmol/L) was well tolerated. This procedure allows the removal of an excess of body sodium and seems to be effective even when conventional ultrafiltration during dialysis has failed. Administration of Captopril either alone or combined with "isovolumetric salt subtraction" induced good control of blood pressure in all 8 patients.

Adolescent↗
PubMed1978

Innappropriate renin secretion unmasked by captopril (SQ 14 225) in hypertension of chronic renal failure.

Captopril (SQ 14 225), an orally active inhibitor of angiotensin-converting enzyme, was given to 7 hypertensive patients with chronic renal failure whose plasma-creatinine ranged from 1.5--7.4 mg/dl; whose plasma-renin activity was normal; whose hypertension was not controlled by previous therapy consisting in 5 patients of three or more antihypertensive drugs; and whose blood-pressures averaged 176/111 +/- 11/3 mm Hg. Inhibition of converting enzyme by oral captopril, 200 mg twice daily, reduced blood-pressure to 156/100 +/- 9/5 mm Hg. 5 patients needed additional treatment by frusemide 40--250 mg/day orally. With this combined regimen the blood-pressure of all patients averaged 126/85 +/- 4/3 mm Hg after 8 +/- 2 weeks of captopril. The drug was well tolerated. These results suggest that inhibition of angiotensin-converting enzyme with or without sodium depletion is an efficient treatment for hypertension associated with chronic renal failure. It appears that although renin levels in patients with this condition may be "normal", they are inappropriate in relation to the subtle degree of sodium retention that occurs with this disorder.

Administration, Oral↗
PubMed1978

Long-term treatment of hypertension in man by an orally active angiotensin-converting enzyme inhibitor.

1. Captopril or SQ 14 225, administered orally twice a day, reduced the blood pressure of hypertensive patients whatever their clinical diagnosis and even when their plasma renin activity was 'normal' or low. 2. Long-term administration of captopril, either alone or together with diuretics, provides a powerful new tool with which to treat ambulatory hypertensive patients. 3. The renin system may play an important role in maintaining blood pressure in a majority of hypertensive patients.

Adult↗
PubMedDate not supplied

Safety and efficacy of chronic therapy with captopril in hypertensive patients: an update.

Captopril, an orally active angiotensin-converting enzyme inhibitor, has been administered to 81 patients with different types of clinical hypertension. Most of the patients had previously uncontrollable high blood pressure. In order to achieve a satisfactory blood pressure control during long-term captopril therapy, a concomitant decrease in total body sodium was required in more than half of the patients. During our first two years of clinical experience with this new antihypertensive agent, side effects developed in 46.9 per cent of the patients and necessitated the withdrawal of the drug in 23.4 per cent of all patients. Only a few side effects such as hypotensive or syncopal episodes and cold extremities appeared to be due to the chronic blockade of the renin-angiotensin system. The most frequent and the most serious adverse reactions such as skin rash, altered taste, pancytopenia, and pemphigus foliaceus seemed to be specifically drug related. The incidence of cutaneous and taste problems was markedly higher in patients with impaired renal function in whom retention of captopril has been previously demonstrated. This suggests that the occurrence of adverse reactions to captopril could be lowered in the future by using smaller daily doses and by titrating them according to the renal function.

Adolescent↗
PubMedDate not supplied

A sensitive and specific two-site, sandwich-amplified enzyme immunoassay for neuropeptide Y.

The development of a new enzyme immunoassay for neuropeptide Y (NPY) is reported. Two monoclonal antibodies directed against distinct epitopes of NPY are used, one as a capture antibody (NPY02) and the other one as an indicator antibody (NPY05), this latter antibody being labeled with alkaline phosphatase. The assay calibration curve was performed over concentrations of 1 to 250 pM in a NPY-free plasma. The intra-assay coefficient of variation (CV) ranged from 0.025 to 11.9%, whereas the interassay CV was comprised between 5 and 12%. The limit of detection of this assay was 1 pM (100 amol/well). Neuropeptide Y levels are related to sampling conditions; basal concentrations of NPY with low SEM are found when less than 1.2 ml of blood is taken in EDTA tubes, the sample is centrifuged at 4 degrees C, and immediately frozen. Unanesthetized spontaneously hypertensive rats exhibited higher NPY plasma concentrations than normotensive Wistar-Kyoto controls (53 +/- 7 pM and 25 +/- 2 pM, respectively, mean +/- SEM, p < 0.01). Plasma NPY levels are similar in 16- and 36-week-old animals. In conclusion, this technique makes it possible to assay a large number of samples within 24 h without requiring radioactivity.

Amino Acid Sequence↗
PubMedDate not supplied

Pre- and postsynaptic effects of SKF64139, a phenylethanolamine N-methyltransferase inhibitor, in conscious normotensive rats.

We investigated in conscious normotensive rats the effect of SKF64139 (2 mg i.v.), a potent phenylethanolamine N-methyltransferase (PNMT) inhibitor, on blood pressure responses to norepinephrine (40, 80, and 160 ng i.v.); methoxamine (2.5, 5 and 10 micrograms i.v.), a directly active sympathomimetic agent that is not taken up by adrenergic nerves; and tyramine (20, 40, and 80 micrograms i.v.), an indirectly acting sympathomimetic amine. The pressor effect of norepinephrine was not changed by 2 mg of SKF64139, while those of methoxamine and tyramine were significantly reduced. The dose-response curve to exogenous norepinephrine was also evaluated following blockade of norepinephrine uptake in the nerve endings using 0.25 mg desipramine i.v. This dose of desipramine had no effect on blood pressure increase induced by methoxamine. In rats pretreated with the neuronal uptake inhibitor desipramine in a dose that did not affect alpha-adrenoceptors, SKF64139 significantly decreased the pressor responses to norepinephrine. Increasing the dose of SKF64139 to 8 mg i.v. resulted in a significant fall in base-line blood pressure and in a blunted blood pressure response to norepinephrine. These data demonstrate that in vivo the PNMT inhibitor SKF64139 blocks alpha-adrenoceptors and inhibits neuronal uptake. The alpha-adrenoceptor blocking properties of SKF65139 are masked by simultaneous blockade of norepinephrine uptake when agonists with affinity for the uptake system are used. These findings need to be taken into account when interpreting cardiovascular effects of the PNMT inhibitor SKF64139.

Animals↗
PubMedDate not supplied

Blood pressure variability in ambulatory hypertensive patients: effect of beta-blocking agents and/or diuretics.

Using a semiautomatic device (Remler), ambulatory blood pressure was recorded in ambulatory hypertensive patients who were either untreated (n = 55) or treated chronically with beta-blocking agents (n = 28), diuretics (n = 42), or a combination of both (n = 75). In all patients, one blood pressure reading was obtained during usual activities every 30 min for 12 h. The selection of untreated patients was based on clinic measurements (two to three repeated blood pressures of greater than 140/89 mm Hg). The mean systolic and diastolic blood pressures averaged from all patients over the whole day did not differ significantly among the groups, ranging from 133.7 to 141 mm Hg for the systolic and from 83.8 to 88.4 mm Hg for the diastolic. The variability of blood pressure, reflected by the difference between the average of the three highest and the three lowest values of the day, was not different among the four groups and ranged from 41.4 to 50.6 mm Hg for the systolic and from 30.1 to 34.4 mm Hg for the diastolic. Similarly, variability expressed as the standard deviation of the mean of all blood pressures measured during the day did not differ among the groups. In all groups, blood pressure was highest in the morning and lowest in early afternoon, and tended to rise again in the late afternoon. Thus, blood pressure variability of hypertensive patients is not changed by antihypertensive therapy with beta-blocking agents and/or diuretics.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Enhanced acute antihypertensive effect of propranolol in the absence of circulating epinephrine in the rat.

beta-Adrenoceptor blocking agents might reduce blood pressure, in part, by blocking presynaptic beta-adrenoceptors. Absence of circulating epinephrine should then reduce the antihypertensive effect of propranolol. Biadrenalectomized Wistar-Kyoto rats were made hypertensive with methylprednisolone (20 mg/kg s.c. weekly), given for 2 weeks, and supplemented with deoxycorticosterone pivalate (10 mg/kg weekly). Sham-operated controls received the same treatment. Baseline weight, mean intraarterial blood pressure, and heart rate of the groups were the same. After propranolol (5 mg/kg s.c.) was administered to the unanesthetized rats, blood pressure fell within 90 min from 151 +/- 4 by 23 +/- 4 mm Hg (mean +/- SEM) in the adrenalectomized animals and from 153 +/- 4 by only 7 +/- 3 mm Hg in the sham-operated controls (p less than 0.001); heart rate fell by 91 +/- 13 beats/min in the adrenalectomized animals and by 40 +/- 11 beats/min in the controls (p less than 0.01). Propranolol's vehicle had no effect. At the end of the experiment, plasma epinephrine levels were less than 40 pg/ml for adrenalectomized rats, and 420 +/- 60 pg/ml for controls. Norepinephrine levels were approximately equal in the two groups. Since blood pressure fell despite virtual absence of circulating epinephrine, these results suggest that propranolol reduces blood pressure, at least in part, by mechanisms other than presynaptic beta-adrenoceptor blockade.

Adrenalectomy↗
PubMedDate not supplied

Blood pressure and heart rate response to central beta-blockade in conscious rats with glucocorticoid-induced hypertension.

The beta-adrenergic antagonist propranolol, administered subcutaneously to conscious adrenalectomized rats made hypertensive by exogenous glucocorticoids, has been shown to induce acutely a marked fall in blood pressure and heart rate. These animals almost completely lacked circulating epinephrine. Because both changes were closely related, it was suggested that in this model of hypertension propranolol acts via a central mechanism. To test this hypothesis, we now administered sotalol (300 micrograms) intracerebroventricularly to unanesthetized adrenalectomized rats with glucocorticoid-induced hypertension (this hydrophilic beta-blocking agent does not cross the blood-brain barrier). The same experiments were also performed in sham-operated glucocorticoid-hypertensive rats. On the day of the study, there was no significant difference between adrenalectomized and sham-operated groups of rats in intraarterial pressure and heart rate. Sotalol increased blood pressure and significantly slowed heart rate during the 60-min observation period, both in adrenalectomized and sham-operated rats. Sotalol's vehicle had no blood pressure effect and caused a transient heart rate acceleration in rats with, as well as without, circulating epinephrine. These results therefore suggest that the previously observed enhanced effect of peripherally administered propranolol in the absence of detectable circulating epinephrine, in this model, is not mediated centrally.

Adrenalectomy↗
PubMedDate not supplied

Dose-dependent effect of atrial natriuretic peptide on blood pressure, heart rate, and skin blood flow of normal volunteers.

Synthetic atrial natriuretic peptide, containing 26 amino acids in the rat sequence, L-364, 343 (Ileu-ANP), was infused intravenously at increasing rates (1-40 micrograms/min) into four normal volunteers. Mean intraarterial blood pressure decreased and heart rate increased in cumulative-dose-dependent fashion. Skin blood flow as measured with a laser Doppler device rose already with a cumulative dose of 55 micrograms Ileu-ANP and further rises were directly related to dose. The only side effects observed were those accompanying symptomatic hypotension at higher doses. These findings provide strong evidence that Ileu-ANP acts as a vasodilator in normal volunteers.

Adult↗
PubMedDate not supplied

Unpredictability of blood pressures recorded outside the clinic in the treated hypertensive patient.

Ambulatory blood pressure profiles were obtained with the Remler M2000, a portable semiautomatic blood pressure recorder, in 38 chronically treated hypertensive patients who continued to have blood pressures measured by their physician greater than 140 mm Hg systolic and greater than 89 mm Hg diastolic. On the average, ambulatory recorded blood pressures were significantly lower (151/94 +/- 26/13 mm Hg; mean +/- SD) than those determined at the clinic not only by a physician (179/109 +/- 22/11 mm Hg), but by a nurse (163/101 +/- 24/10 mm Hg). Individual mean recorded ambulatory blood pressures could be predicted neither from office readings obtained by a physician nor from those measured by a nurse. Because of this unpredictability of blood pressures prevailing outside the clinic, ambulatory blood pressure monitoring seems to be very useful, if not necessary, in assessing the efficacy of antihypertensive drugs. By this technique, it may be possible to select patients who do not need a change of treatment although their blood pressure levels remain persistently elevated in the physician's office.

Blood Pressure Determination↗
PubMedDate not supplied

Discrepancy between antihypertensive effect and angiotensin converting enzyme inhibition by captopril.

Captopril, an inhibitor of angiotensin converting enzyme, was administered twice daily to 13 hypertensive patients for a mean period of 9 weeks. Continuous blood pressure control in the ambulatory patients was established with a portable blood pressure recorder. Notwithstanding, in eight patients with normal renal function, plasma converting enzyme was found to resume normal activity before administration of the morning dose of captopril. Only in 5 patients with impaired renal function did some blockade of plasma converting enzyme persist for more than 12 hours. Measured plasma converting enzyme activity seemed to reflect total conversion of angiotensin I, including conversion in the pulmonary vascular bed, since changes in its activity were closely paralled by changes in plasma aldosterone levels. Bradykinin accumulation seems unlikely when converting enzyme and thus, presumably, kininase II has resumed normal activity. Captopril administration does not seem to alter plasma epinephrine or norepinephrine levels. Blood pressure reduction in the face of normal angiotensin converting enzyme activity is probably due to hyporesponsiveness of the arterioles to pressor hormones, which may be due to specific renin-related and/or nonspecific effects of captopril.

Adult↗
PubMedDate not supplied

Role of reactive hyperreninemia in blood pressure changes induced by sodium depletion in patients with refractory hypertension.

Sixteen patients with refractory hypertension were submitted to vigorous sodium depletion while cardiovascular homeostasis was monitored with measurements of hormonal and hemodynamic parameters and repeat saralasin tests. This regimen resulted in a negative sodium balance by an average of 300 mEq. The loss of sodium closely correlated to the decrease of body weight (r = 0.70, p less than 0.005). Blood pressure (BP) decreased from 176/166 +/- 8/3 to 155/109 +/-6/3 mm Hg. There was a significant correlation between percent increments in plasma renin activity (PRA) and the rise in plasma norepinephrine (r = 0.68, p less than 0.05) and a close negative correlation between percent increase in PRA and the ratio of fall in mean blood pressure (MAP) per unit of weight loss (r = -0.73, p less than 0.005). Thus, patients with the least percent increase in PRA demonstrated the greatest fall in BP per unit of weight loss, indicating that relative rather than absolute elevation of renin may be the factor limiting antihypertensive efficacy of sodium depletion. Sodium depletion induced increase in peripheral resistance and decrease in cardiac output, both mostly attributable to relative hyperreninemia. Indeed, the adverse hemodynamic changes were reversed by angiotensin inhibition, during which BP normalized. It is concluded that vigorous sodium depletion complemented by angiotensin blockade or suppression with sympatholytic agents improves management of otherwise refractory hypertension.

Adult↗