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Biomedical subjects

B Waeber

Publications and source records attributed to B Waeber.

At least 181 records · Page 10Linked to original sources
PubMed1991

Effect of weight reduction in moderately overweight patients on recorded ambulatory blood pressure and free cytosolic platelet calcium.

Although platelet cytosolic calcium has been shown to decrease during pharmacological treatment of hypertension, there is no evidence that cytosolic calcium also falls during a nonpharmacological reduction in blood pressure. To provide such evidence, we examined prospectively the relation between platelet cytosolic calcium and ambulatory blood pressure during weight reduction in moderately overweight (body mass index [BMI] greater than 25), mildly hypertensive individuals. The experimental group (responders: BMI reduction greater than 5%) consisted of 19 patients who lost 8.5 +/- 2.9 kg (mean +/- SD, p less than 0.05) during a 10-week hypocaloric diet, whereas the control group (nonresponders: BMI reduction less than 5%) consisted of 12 patients who showed no relevant change in body weight (-2.0 +/- 1.3 kg) during the same period of time. The moderate weight loss of the responders decreased blood pressure by 14/5 mm Hg (p less than 0.05), as measured by ambulatory monitoring, which renders a placebo effect unlikely. This nonpharmacological reduction in blood pressure was accompanied by a proportional 11% decrease (p less than 0.05) in platelet cytosolic calcium and also by significant (p less than 0.05) decreases in plasma catecholamines and serum cholesterol. These findings establish the concept of a nonpharmacological reduction in free cytosolic platelet calcium in humans and add further evidence suggesting a link between intracellular calcium homeostasis and blood pressure regulation.

Blood Platelets↗
PubMed1991

Oral administration of DuP 753, a specific angiotensin II receptor antagonist, to normal male volunteers. Inhibition of pressor response to exogenous angiotensin I and II.

BACKGROUND: The purpose of the present study was to assess the inhibitory effect of DuP 753, an orally active angiotensin II receptor antagonist, on the pressor action of exogenous angiotensin I and II in healthy male volunteers. METHODS AND RESULTS: In the first study (single-dose study), eight volunteers were included in a 2-day protocol repeated four times at 1-week intervals. In each phase, a different dose of drug (2.5, 5, 10, 20, or 40 mg) or placebo was given. The peak systolic blood pressure response to a test-dose of angiotensin I was determined serially before and after oral administration of DuP 753 by continuously monitoring finger blood pressure using a photoplethysmographic method. DuP 753 reduced the systolic blood pressure response to angiotensin I in a dose-dependent fashion. Three, 6, and 13 hours after the 40-mg dose, blood pressure response decreased to 31 +/- 5%, 37 +/- 6%, and 45 +/- 3% of the control values (mean +/- SEM, n = 7), respectively. In the second study, 29 volunteers were treated for 8 days with either a placebo or DuP 753 (5, 10, 20, or 40 mg p.o. q.d.) and challenged on the first, fourth, and eighth days with bolus injections of angiotensin II. Again, the inhibitory effect on the systolic blood pressure response to angiotensin II was clearly dose dependent. Six hours after 40 mg DuP 753, the systolic blood pressure response to the test-dose of angiotensin II was reduced to 37 +/- 7%, 40 +/- 4%, and 38 +/- 6% of baseline values (mean +/- SEM, n = 6) on days 1, 4, and 8, respectively. With this latter dose, there was still a blocking effect detectable 24 hours after the drug. Similar to angiotensin converting enzyme and renin inhibitors, DuP 753 induced a dose-dependent increase in plasma renin that was more pronounced on the eighth than on the first day of drug administration. In these normal volunteers, no consistent clinically significant side effects were observed. There was no evidence for an agonist effect. CONCLUSIONS: DuP 753 appears to be a well-tolerated, orally active, potent, and long-lasting antagonist of angiotensin II in men.

Administration, Oral↗
PubMed1991

Antihypertensive therapy and mobilization of renal functional reserve.

The normal kidney can increase its rate of glomerular filtration in response to an acute protein load. It has been suggested that this acute hyperfiltration represents a renal functional reserve (RFR). The RFR has also been proposed to reflect the chronic hyperfiltration found in diabetic patients and animal models of chronic renal failure. The physiologic role of the RFR is still unclear. On the one hand, the availability of an RFR may retard the progression towards end-stage renal failure. On the other hand, sustained hyperfiltration has been implicated as a potential deleterious factor in the progression of renal disease. Antihypertensive drugs used in the management of hypertensive patients with chronic renal disease modify both the systemic and the renal hemodynamics. Depending on their hemodynamic effects, they may thereby alter the ability to mobilize RFR. Today, it is still not clear whether an ideal compound should increase, decrease, or not affect RFR to preserve long-term renal function. Evaluation of the effects of various antihypertensive agents on RFR could become an important aspect of consideration in order to optimize both the control of blood pressure and the capacity of the therapy to prevent deterioration of renal function.

Adrenergic beta-Antagonists↗
PubMed1991

Calcium antagonists as first-line therapy in hypertension: results of the Swiss Isradipine Study. Swiss Hypertension Society.

In this study of the efficacy and safety of isradipine as first-line therapy in hypertension, 1,647 patients enrolled; 1,472 completed the 4-week placebo run-in period and began treatment with isradipine at 2.5 mg twice daily for 4 weeks. During placebo, 11% (n = 175) of the 1,647 patients withdrew because of normalization of blood pressure, side effects, noncompliance, violation of the study protocol, side effects from concomitant therapy, or other reasons. During isradipine therapy (n = 1,376), blood pressure decreased from 168 +/- 18/102 +/- 8 mm Hg at the end of the placebo period to 155 +/- 17/94 +/- 9 mm Hg after 2 weeks (p less than 0.001) and 151 +/- 16/92 +/- 9 mm Hg after 4 weeks (p less than 0.001). During active treatment, 6.4% (n = 94) were withdrawn because of flushing, headache, edema, palpitations, gastrointestinal side effects, skin rashes, or other side effects, and two patients because of lack of efficacy. The side effect score in the remaining patients worsened for flushing, remained unchanged for edema, but significantly improved for palpitations, fatigue, dizziness, headache, and nervousness. After 4 weeks, 60% of patients had diastolic blood pressures of less than or equal to 90 mm Hg. Thus, isradipine is effective and safe as first-line therapy in patients with primary hypertension as seen in general practice.

Aged↗
PubMed1991

Ambulatory blood pressure monitoring in children, adolescents and elderly people.

Non-invasive ambulatory blood pressure monitoring is increasingly being used in the diagnosis and the treatment of adult hypertensive patients. In children, the most obvious clinical use for intermittent blood pressure recordings is in the evaluation of borderline hypertension and the assessment of the efficacy of antihypertensive therapy. Adolescents who are hypertensive in the presence of the doctor are more often normotensive outside the physician's office than adult and elderly patients. Many elderly patients with isolated systolic hypertension have normal ambulatory systolic readings. Elderly patients with high blood pressures only in the physician's presence generally do not show a fall in ambulatory blood pressures when antihypertensive therapy is initiated or intensified. Thus, ambulatory blood pressure monitoring may be useful in detecting truly hypertensive patients among children and adolescents and in elderly people. This technique should make it possible to better define the cardiovascular risk, to avoid overtreatment and to individualize antihypertensive therapy.

Adolescent↗
PubMed1991

Evaluation of antihypertensive therapy: discrepancies between office and ambulatory recorded blood pressure.

Non-invasive ambulatory blood pressure monitoring has proved to be very useful in investigating hypertensive patients. So far, almost everything known about this technique is based on studies performed in specialized centers. We summarize here the results of two trials in which private physicians used ambulatory blood pressure monitoring to assess the efficacy of antihypertensive drugs. The results found in this clinical setting were very similar to those observed previously in specialized clinics. In the individual patient, the level of ambulatory recorded pressure could not be predicted from blood pressure readings taken at the doctor's office. Furthermore, the blood pressure response to antihypertensive therapy was more reproducible when evaluated by ambulatory blood pressure monitoring than by the doctor. It appears, therefore, that non-invasive ambulatory blood pressure monitoring is also useful in everyday practice for the management of hypertensive patients.

Antihypertensive Agents↗
PubMed1991

[Non invasive measurement of arterial compliance].

Pulse pressure waves are damped by the elastic properties of the blood vessels. This damping capacity can be evaluated by measuring vascular compliance a parameter which expresses changes of volume with respect to changes of pressure. Arterial compliance varies continuously with respect to intravascular pressure. Our group has developed an ultrasonograph which functions in the A mode capable of measuring the diameter of peripheral arteries during the cardiac cycle. This system is coupled to a photoplethysmograph which records non-invasively and continuously finger blood pressure. This enables construction of pressure-diameter graphs and the determination of arterial compliance and distensibility at each pressure value.

Arteries↗
PubMed1990

Neuropeptide Y: a missing link?

Yet another 'orphan' molecule that had to find its place in life after isolation and sequencing, neuropeptide Y appears to be an important cardiovascular neuroregulator and also links the sympathetic and renin-angiotensin systems. The peptide's physiologic and pathophysiologic roles, as well as its potential therapeutic value, are examined.

Animals↗
PubMed1990

[Angiotensin-converting-enzyme inhibition in arterial hypertension].

Angiotensin converting enzyme (ACE) inhibitors were developed to prevent the generation of angiotensin II and thereby to reduce peripheral vasoconstriction. These drugs have already proven their efficacy in the management of essential hypertension as well as of various forms of secondary hypertension. When given alone or in combination with other antihypertensive agents, they allow to normalize blood pressure of almost all patients. These compounds have favorable effects on hemodynamics and regional blood flow distribution. They do not affect lipid metabolism and have usually no deleterious influence on the quality of life. In view of their efficacy and tolerability profile, ACE inhibitors are likely to become widely used as first choice antihypertensive agents.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Influence of sodium balance on atrial natriuretic factor in rats with one-kidney, one-clip renal hypertension.

The influence of sodium intake on the gene expression and circulating levels of atrial natriuretic factor (ANF) was investigated in unanesthetized rats with one-kidney, one-clip renal hypertension. After clipping, the rats were maintained for 3 weeks either on a salt-deficient (n = 11) or a regular-sodium diet (n = 10). Animals which had received the regular-sodium diet exhibited significantly higher ANF mRNA levels in their right and left atria than salt-restricted animals, whereas there was no significant difference in plasma ANF levels.

Animals↗
PubMed1990

Noninvasive blood pressure monitoring at the finger for studying short lasting pressor responses in man.

The study of vasoactive agents in man often requires accurate measurement of short-lasting changes in blood pressure. Using a noninvasive photoplethysmographic device (Finapres), the authors investigated in normotensive subjects whether rapid increases in blood pressure can be assessed precisely by monitoring finger blood pressure continuously. Six volunteers were studied on two consecutive days. On the first day, increasing doses of angiotensin I were injected intravenously with the aim to find a test dose which raised systolic blood pressure by 25 to 40 mm Hg. After oral administration of a placebo, the same test dose was injected repeatedly over the next 24 hours. On the second day, the subjects took either 6.25 (n = 3) or 25 mg (n = 3) captopril PO and the serial administration of the test dose of angiotensin I was continued for the next 4 hours. After placebo intake there was a good reproducibility of the blood pressure response to angiotensin I with a coefficient of variation of 15 +/- 4.5% (Mean +/- SD, n = 6). Captopril caused a dose-dependent inhibition of the pressor effect of angiotensin I. These data indicate that noninvasive blood pressure monitoring at the finger represents a useful tool to study short-lasting blood pressure changes produced by vasoactive agents in man.

Adult↗
PubMed1990

Treating the individual hypertensive patient: considerations on dose, sequential monotherapy and drug combinations.

For the general practitioner to be able to prescribe optimal therapy to his individual hypertensive patients, he needs accurate information on the therapeutic agents he is going to administer and practical treatment strategies. The information on drugs and drug combinations has to be applicable to the treatment of individual patients and not just patient study groups. A basic requirement is knowledge of the dose-response relationship for each compound in order to choose the optimal therapeutic dose. Contrary to general assumption, this key information is difficult to obtain and often not available to the physician for many years after marketing of a drug. As a consequence, excessive doses are often used. Furthermore, the physician needs comparative data on the various antihypertensive drugs that are applicable to the treatment of individual patients. In order to minimize potential side effects due to unnecessary combinations of compounds, the strategy of sequential monotherapy is proposed, with the goal of treating as many patients as possible with monotherapy at optimal doses. More drug trials of a crossover design and more individualized analyses of the results are badly needed to provide the physician with information that he can use in his daily practice. In this time of continuous intensive development of new antihypertensive agents, much could be gained in enhanced efficacy and reduced incidence of side effects by taking a closer look at the drugs already available and using them more appropriately in individual patients.

Antihypertensive Agents↗
PubMed1990

Prevention of renal hypertension in the rat by neuropeptide Y.

Neuropeptide Y is known to enhance blood pressure responsiveness to various constrictors, including angiotensin II, and to suppress renin secretion. This study was undertaken to assess the effect of neuropeptide Y on the development of two-kidney, one clip renal hypertension. Normotensive rats either had a silver clip placed on the left renal artery or were sham-operated upon. An osmotic minipump, which was connected via a catheter to a jugular vein, was implanted subcutaneously in all rats. These pumps delivered either neuropeptide Y (0.001 microgram/min) or saline intravenously. Eight days later, an intra-arterial catheter was inserted and the rats were studied while not anesthetized on the following day. Neuropeptide Y did not affect body weight. In clipped rats, neuropeptide Y prevented the development of hypertension and suppressed renin secretion. Neuropeptide Y significantly decreased blood pressure also in sham-operated rats, although it had no effect on plasma renin activity. These data indicate that prolonged neuropeptide Y infusion may lower blood pressure by different mechanisms, one of which is probably a suppression of renin release.

Animals↗
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↗