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Biomedical subjects

B Waeber

Publications and source records attributed to B Waeber.

At least 145 records · Page 8Linked to original sources
PubMed1993

The renin-angiotensin system and arterial wall behavior.

To assess the behavior of the arterial wall in hypertensive patients, we developed a noninvasive ultrasonic device. Simultaneous recordings of internal diameter and blood pressure over the whole cardiac cycle are used to establish compliance-pressure curves. Blood pressure, which is a co-determinant of compliance, is thus taken into account. This method allows one to compare arteries from patients with different blood pressures. Arterial compliance and distensibility were first investigated in healthy young volunteers administered either lisinopril (20 mg), atenolol (100 mg) or nitrendipine (20 mg) once a day. After 8 days of treatment, only lisinopril was found to increase arterial compliance. Subsequently, we compared arterial diameter- and distensibility-pressure curves from newly diagnosed and untreated hypertensive patients with those of matched normotensive control patients. Diameter-pressure curves did not differ significantly between the groups and distensibility was not reduced. Similar findings were later obtained in an animal model, when mechanical properties of carotid arteries were compared between spontaneously hypertensive rats and normotensive counterparts (Wistar-Kyoto rats). These results, although interesting by providing noninvasive information on the elastic response of the wall, call for further development of the technique to be able to measure arterial wall thickness. Stress-strain relationship could ultimately be established to thoroughly characterize physical properties of blood vessel walls.

Animals↗
PubMed1993

Neuropeptide Y and cardiovascular regulation.

Neuropeptide Y is a vasoactive peptide and is widely distributed throughout the central and peripheral nervous systems. Neuropeptide Y is co-released with noradrenaline by perivascular nerve endings. At high concentrations, it has a direct vasoconstrictor effect. In addition, it enhances the vascular effect of various agonists, including noradrenaline and angiotensin II. Moreover, neuropeptide Y has an inhibitory effect on renin secretion. This peptide may have an important role in cardiovascular regulation.

Animals↗
PubMed1993

Spontaneous diameter oscillations of the radial artery in humans.

In this study we investigated whether there exists a periodic contractile activity of the radial artery, and we evaluated the impact of such an oscillatory behavior on the mechanical properties of this medium-sized muscular vessel. The internal diameter of the right radial artery was measured noninvasively in six healthy male volunteers aged 18-42 yr using a high-precision ultrasonic echo-tracking device. Blood pressure was simultaneously recorded on the same side at the middle finger by photoplethysmography. The electrical activity of the heart was monitored during the entire experiment by electrocardiography. The frequency components of the arterial diameter, blood pressure, and heart rate were obtained using spectral analysis. Under resting conditions, the radial arterial diameter exhibited a spontaneous oscillation with a period ranging from 45 to 70 s and an amplitude of 80 +/- 14 microns (+/- SE). No very low-frequency mode (< or = 0.02 Hz) was identified in either heart rate or blood pressure. These diameter oscillations affected the distensibility-pressure curves acquired simultaneously. Thus the 3-4% oscillatory variation in arterial diameter was paralleled by a 1.5- to 2-fold change in distensibility. These low-frequency oscillations of large arteries seem to be mediated by an intrinsic vascular mechanism.

Adolescent↗
PubMed1993

Salt-dependent renal effects of an angiotensin II antagonist in healthy subjects.

This study was designed to evaluate in healthy volunteers the renal hemodynamic and tubular effects of the orally active angiotensin II receptor antagonist losartan (DuP 753 or MK 954). Losartan or a placebo was administered to 23 subjects maintained on a high-sodium (200 mmol/d) or a low-sodium (50 mmol/d) diet in a randomized, double-blind, crossover study. The two 6-day diet periods were separated by a 5-day washout period. On day 6, the subjects were water loaded, and blood pressure, renal hemodynamics, and urinary electrolyte excretion were measured for 6 hours after a single 100-mg oral dose of losartan (n = 16) or placebo (n = 7). Losartan induced no significant changes in blood pressure, glomerular filtration rate, or renal blood flow in these water-loaded subjects, whatever the sodium diet. In subjects on a low-salt diet, losartan markedly increased urinary sodium excretion from 115 +/- 9 to 207 +/- 21 mumol/min (P < .05). The fractional excretion of endogenous lithium was unchanged, suggesting no effect of losartan on the early proximal tubule in our experimental conditions. Losartan also increased urine flow rate (from 10.5 +/- 0.4 to 13.1 +/- 0.6 mL/min, P < .05); urinary potassium excretion (from 117 +/- 6.9 to 155 +/- 11 mumol/min); and the excretion of chloride, magnesium, calcium, and phosphate. In subjects on a high-salt diet, similar effects of losartan were observed, but the changes induced by the angiotensin II antagonist did not reach statistical significance. In addition, losartan demonstrated significant uricosuric properties with both sodium diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Neuropeptide Y expression and regulation in a differentiated rat insulin-secreting cell line.

Neuropeptide-Y (NPY) is a 36-amino acid peptide known to inhibit glucose-stimulated insulin secretion in various animal models in vitro and in vivo. NPY is thought to be one of the mediators of sympathetic action in the pancreas through nerve endings surrounding the islets, and it has recently been shown to be synthesized within the islets of Langerhans. To elucidate the potential role of NPY in the endocrine pancreas, we studied the expression and regulation of NPY secretion in a rat insulinoma cell line (INS-1). NPY mRNA and peptide are highly expressed and secreted by INS-1 cells. NPY levels were determined by a sensitive and specific two-site amplified enzyme-linked immunosorbent assay. Incubation of INS-1 cells with various glucose concentrations did not modify NPY secretion; however, stimulation of adenylate cyclase by forskolin induced a dose- and time-dependent increase in NPY release in the medium. The glucagon-like peptide-I-(7-36) amide (GLP-1), a known gluco-incretin in humans, induced at low concentration (10(-9) M) a similar expression of NPY mRNA and peptide secretion in INS-1 cells. On the other hand, the inhibition of cAMP accumulation by the alpha 2-adrenergic agonist clonidine decreased NPY secretion. In conclusion, 1) high levels of gene expression and secretion of NPY are found in a rat insulinoma cell line (INS-1). 2) Accumulation of cAMP induced by forskolin or a gluco-incretin (GLP-1) induces a further increase in NPY gene expression and release. 3) NPY secretion is not modulated by low or high glucose concentrations in the medium. 4) Induction of NPY, a known inhibitor of insulin secretion, may represent a novel counterregulatory mechanism of insulin secretion, limiting the stimulatory effect of GLP-1 on insulin secretion.

Adenylyl Cyclases↗
PubMed1993

Angiotensin II antagonists.

Acute blockade of the renin-angiotensin system with the parenterally active angiotensin II antagonist saralasin has been shown to effectively lower blood pressure in a large fraction of patients with essential hypertension and to improve hemodynamics in some patients with congestive heart failure. It is now possible to antagonize chronically angiotensin II at its receptor using the non-peptide angiotensin II inhibitor losartan (DuP 753, MK 954). When administered by mouth, this compound induces a dose-dependent inhibition of the pressor response to exogenous angiotensin II. This effect is closely related to circulating levels of the active metabolite E3174. Preliminary studies performed in hypertensive patients suggest that losartan has a blood pressure lowering action equivalent to that of an ACE inhibitor. Whether this compound will compare favorably with ACE inhibitors requires however further investigation.

Angiotensin II↗
PubMed1993

Ambulatory blood pressure monitoring to assess antihypertensive therapy in private practice.

Non-invasive ambulatory blood pressure monitoring has proved to be very useful in evaluating hypertensive patients. However, most previous studies were performed in specialised centres. Here the results of two trials are presented in which private physicians used ambulatory BP monitoring to assess the efficacy of antihypertensive drugs. The results were very similar to those observed previously in specialised clinics. In the individual patient, the level of ambulatory recorded pressure could not be predicted based on BP readings taken at the doctor's office. Also, the BP response to antihypertensive therapy was more reproducible when evaluated by ambulatory BP monitoring than by the doctor. Thus, the use of noninvasive ambulatory BP monitoring is also very appropriate in everyday practice for the management of hypertensive patients.

Ambulatory Care↗
PubMed1993

Control of vascular tone by renin and angiotensin in cardiovascular disease.

The tools which have led to a better understanding of the role of the renin-angiotensin system in determining the tone of peripheral arteries in cardiovascular disease consist of highly specific and sensitive methods to measure the different components of the renin-angiotensin system and in specific probes used to inhibit the renin-angiotensin system at several points of the enzymatic cascade. The therapeutic efficacy of these more and more specific probes undoubtedly provides strong circumstantial evidence that angiotensin II plays an important role in determining peripheral vascular tone. While this has considerably increased our understanding of the regulatory mechanism involved in blood pressure maintenance in normotensive subjects and hypertensive patients, the role of the renin-angiotensin system as an aetiological factor in the development of essential hypertension still remains unclear.

Angiotensin II↗
PubMed1993

Angiotensin II blockade compared with other pharmacological methods of inhibiting the renin-angiotensin system.

AIM: To compare angiotensin II receptor blockade, angiotensin converting enzyme (ACE) inhibition and renin inhibition as pharmacological methods of inhibiting the renin-angiotensin system. METHOD: Review of published results of studies using the three methods, with a particular emphasis on measurement problems. RESULTS: Whenever an attempt is made to block the renin-angiotensin system, by whatever approach, there is a compensatory rise in renin secretion which determines the effect of the drug. Accurate biochemical methods must be available to assess the efficacy of each approach. ACE inhibitors have been very successful and are generally well tolerated but cough is a common side effect, possibly related to their lack of specificity. High doses stimulate renin secretion. Renin inhibitors are theoretically more attractive than ACE inhibitors because of their specificity, and renin inhibitors with adequate oral bioavailability are now available. Due to the reactive rise in renin, however, the effects of the renin inhibitors so far available appear to be very short in duration. There is insufficient evidence to show whether prolonged administration may be successful. With present methods, only circulating angiotensin I and II levels can give an accurate indication of the effectiveness of the drug. The first non-peptide angiotensin II inhibitor, losartan (DuP753, MK 954), is still undergoing clinical trials. Dose-dependent inhibition of the pressor response to exogenous angiotensin II has been obtained in normotensive volunteers, the effect being closely related to circulating levels of the active metabolite E 3174. The reactive rise in plasma renin activity and angiotensin II was highly variable. A preliminary study in hypertensive patients showed effective blood pressure reduction at doses based on the results obtained in normotensive volunteers. CONCLUSIONS: Renin inhibitors and angiotensin antagonists represent potentially exciting alternatives to the ACE inhibitors. At present, only orally active angiotensin II antagonists are available for extensive clinical evaluation, and the results so far look promising. Whether these compounds will compare favourably with ACE inhibitors requires further investigation.

Angiotensin Receptor Antagonists↗
PubMed1993

Inhibitors of the renin-angiotensin system.

Inhibition of the renin-angiotensin system with angiotensin-converting enzyme inhibitors is well established as a treatment modality for hypertension and congestive heart failure. While converting enzyme inhibitors are well tolerated, they still have some side effects, which rightly or wrongly are attributed to the lack of specificity of the target enzyme for the renin-angiotensin cascade. The attempt is therefore made to inhibit the more specific enzyme renin or to block the angiotensin II receptor. While so far renin inhibitors are generally hampered by insufficient oral bioavailability, potent orally active angiotensin II antagonists are currently in clinical development. Both pharmacologic principles, renin inhibition and angiotensin II antagonism, have been shown to actively reduce blood pressure of hypertensive patients. It remains to be seen whether these newer compounds will be able to replace the converting enzyme inhibitors and exhibit even fewer untoward effects.

Angiotensin II↗
PubMed1992

[What have we learned from converting enzyme inhibitors on renin-angiotensin system?].

Angiotensin-converting-enzyme (ACE) inhibitors are now widely used to treat patients with high blood pressure or heart failure. The favourable results obtained with these inhibitors of the renin-angiotensin system suggest that angiotensin II has a noxious effect on the development and/or course of these diseases. ACE inhibitors are usually well tolerated. Their most severe side-effects are mostly foreseeable and therefore avoidable. Chronic blockade of the renin-angiotensin system increasingly seems to be a good therapeutic approach to the protection of the vital organs.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

[Evaluation of the antihypertensive efficacy of isradipine SRO as assessed by ambulatory blood pressure determination].

The calcium channel blocker isradipine has become recently available in a form with delayed release (isradipine SRO). The anti-hypertensive efficacy and tolerance of this preparation at a single daily dose of 5 mg was studied in 40 patients with uncomplicated essential hypertension over a period of 6 weeks. Blood pressure during office visits decreased under Isradipine SRO from 164/105 +/- 16/7 to 144/93 +/- 12/7 mmHg (mean +/- 1 standard deviation p < 0.001). Using ambulatory blood pressure recording we could show that antihypertensive efficacy of the new galenic form persisted over 24 hours. During the day the blood pressure dropped from 150/95 +/- 13/7 to 141/91 +/- 13/7 mmHg (p < 0.001), during the night from 131/85 +/- 13/3 to 121/81 +/- 15/9 mmHg (p < 0.001). Heart-rate was not changed by treatment and the drug was well tolerated. Isradipine SRO at a single dose is thus well suited for antihypertensive treatment.

Adult↗
PubMed1992

A novel cyclic analog of neuropeptide Y specific for the Y2 receptor.

The low-molecular-mass, cyclic analog of neuropeptide Y, [Ahx5-24, gamma-Glu2-epsilon-Lys30] NPY (YESK-Ahx-RHYINKITRQRY; Ahx, 6-aminohexanoic acid; NPY, neuropeptide Y), was synthesized and investigated for receptor binding, inhibition of forskolin-stimulated cAMP accumulation, inhibition of electrically stimulated rat vas deferens contractions and ability to increase blood pressure. Like the linear peptide [Ahx5-24] NPY (YPSK-Ahx-RHYINLITRQRY), the more rigid, cyclic analog showed good correlation between receptor binding to rabbit kidney membranes and biological activity in the vas deferens assay. Binding of this peptide to a new Y2-receptor-expressing cell line was slightly reduced, compared to the linear peptide [Ahx5-24] NPY, however inhibition of cAMP accumulation was even more efficient. Unlike the linear peptide [Ahx5-24] NPY, the cyclic analog did not induce a blood pressure increase in rats. Reduced binding to Y1 receptor-expressing SK-N-MC cells, as well as the loss of capability of signal transduction, suggest that only Y2-mediated activity is preserved after cyclization. The selectivity of the cyclic compound for Y2 subtypes of NPY receptors with respect to inhibition of cAMP accumulation is more than fortyfold increased, as compared to the linear NPY-(13-36) peptide, which has been used to determine Y2 selectivity so far.

Amino Acid Sequence↗
PubMed1992

[Preliminary evaluation of the Profilomat, a new portable blood pressure recorder].

Ambulatory blood pressure monitoring is increasingly used in clinical evaluation of the hypertensive patient. The aim of the present study is to investigate the accuracy of non-invasive blood pressure measurements provided by the Profilomat, a new portable, automatic blood pressure recorder, in normotensive subjects and hypertensive patients. The results showed a good correlation between the blood pressure values measured by this apparatus and those determined simultaneously by the conventional auscultatory method (sphygmomanometer). Thus, the Profilomat appears to be a useful instrument for study of arterial blood pressure outside the doctor's office.

Adult↗
PubMed1992

[Practical consequences blood pressure variability].

Arterial pressure varies over the course of the day depending on activities. It increases frequently in the presence of the physician. Long term blood pressure recording makes available a multitude of measurements taken during usual activities of the patient. These measurements permit identification of hypertensive patients at high risk i.e. patients with high blood pressure not only when facing their physician.

Blood Pressure↗
PubMed1992

Drug concentration response relationships in normal volunteers after oral administration of losartan, an angiotensin II receptor antagonist.

The aim of this study was to investigate the relationships between plasma concentrations of losartan, an orally active angiotensin II inhibitor, its active metabolite EXP3174, and angiotensin II blockade. Six healthy subjects received single oral doses of 40, 80, or 120 mg losartan and placebo at 1-week intervals in a crossover study. Angiotensin II blockade was assessed by the blood pressure response to exogenous angiotensin II before and after losartan administration. EXP3174 reached higher plasma concentrations and was eliminated more slowly than its parent compound; its levels paralleled the profile of angiotensin II blockade closer than losartan. Inhibition of the pressure response was dose dependent. The Hill-shaped relationship between response and EXP3174 concentration (or time-integrated variables) approached a plateau with 80 mg. The dose-dependent increase in plasma renin and angiotensin II exhibited a considerable individual scatter. We conclude that losartan produces a dose-dependent, effective angiotensin II blockade that is largely determined by the active metabolite EXP3174.

Administration, Oral↗