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Biomedical subjects

B Waeber

Publications and source records attributed to B Waeber.

At least 127 records · Page 7Linked to original sources
PubMed1994

Value of different clinical and biochemical correlates to assess angiotensin converting enzyme inhibition.

In a double-blind study, we compared the value of different approaches to assess blockade of angiotensin (Ang) II generation in 10 normal volunteers treated with the new Ang-converting enzyme (ACE) inhibitor temocapril. Plasma concentration of the diacid active metabolite of temocapril, plasma Ang I and II levels, plasma ACE activity, and inhibition of the pressor response to repeated intravenous (i.v.) doses of Ang I were measured before and repeatedly after different doses of tempocapril or placebo. In vivo ACE activity, estimated by the plasma Ang II/Ang I ratio, correlated well with temocapril diacid concentration (r = 0.85, n = 148) and with systolic and diastolic blood pressure (SBP, DBP) responses to Ang I (r = 0.76 and r = 0.79, n = 148). SBP and DBP responses to Ang I were also strongly related to temocapril diacid concentration (r = -0.81 and r = -0.88, n = 148). ACE activity measured in vivo reliably predicts the decrease in Ang-dependent BP to be achieved by ACE inhibitors.

Administration, Oral↗
PubMed1994

Neuropeptide Y infusion decreases plasma renin activity in postmyocardial infarction rats.

We wished to determine if chronic neuropeptide Y (NPY) infusion (1 ng/min for 1 week by Alzet minipump) could decrease plasma renin activity (PRA) and norepinephrine (NE) in a rat myocardial infarction (MI) model of moderate compensated congestive heart failure (CHF). CHF was produced by prior (6-8 weeks) ligation of the left coronary artery; control rats were sham-operated. Carotid arterial blood was drawn for PRA and NE in conscious unrestrained rats that had been instrumented 24 h earlier. MI rats had increased PRA as compared with sham-operated rats [8.73 +/- 1.27 vs. 5.10 +/- 0.91 ng angiotensin (AI) I/ml.h, mean +/- SE]. During chronic NPY infusion, PRA was reduced to normal in the MI group (4.78 +/- 0.91) but was not affected in the sham group (5.65 +/- 0.51). Plasma NE was altered similarly, but the changes did not reach statistical significance. These data suggest that NPY has the capacity to restrain renin release in moderate compensated CHF.

Animals↗
PubMed1994

Mechanisms of the pressor response to intravenous thyrotropin-releasing hormone in the rat.

1. The purpose of this study was to examine the contribution of the sympatho-adrenomedullary system to the blood pressure response to an intravenous bolus of thyrotropin-releasing hormone (TRH) in conscious medullectomized and sham-operated rats. 2. The peak pressor effect of 0.5 mg TRH was significantly increased in rats having no adrenal medulla (+24.2 +/- 1.6 mmHg, mean +/- s.e.m., P < 0.01) as compared to sham-operated animals (+12.2 +/- 3.0 mmHg). 3. Blockade of alpha-adrenergic receptors with phentolamine abolished the pressor effect of TRH in control rats (+2.1 +/- 1.9 mmHg) but did not attenuate the blood pressure response of medullectomized rats (+21.5 +/- 4.7 mmHg). In contrast, beta-blockade with propranolol blunted the blood pressure responsiveness of rats subjected to adrenal medullectomy (+12.4 +/- 2.6 mmHg) but did not modify the effect of TRH in sham-operated controls (+10.9 +/- 2.9 mmHg). 4. The direct in vitro effect of TRH on isolated mesenteric rat arteries was also evaluated. TRH did not induce contractions of isolated arteries. 5. These results suggest that in rats with intact adrenals, the pressor effect of intravenous TRH is mediated primarily by a stimulation of alpha-adrenergic receptors. Adrenal medullectomy appears to enhance the blood pressure response to intravenous TRH. Activation of cardiac beta-adrenoceptors seems to contribute to the blood pressure increasing effect of intravenous TRH in medullectomized animals.

Acetylcholine↗
PubMed1994

Long-term nitric oxide synthase inhibition and distensibility of carotid artery in intact rats.

The goal of the present study was to evaluate the effect of long-term nitric oxide synthase inhibition by NG-nitro-L-arginine-methyl ester (L-NAME) on the morphology and viscoelastic properties of the carotid arteries in rats. Twelve-week-old Wistar-Kyoto rats were treated for 6 weeks with either the nitric oxide synthase inhibitor L-NAME (0.4 g/L in drinking water; L-NAME rats, n = 13) or tap water (control rats, n = 13). Age-matched spontaneously hypertensive rats (SHR, n = 14) received tap water for the same period. The internal diameter of the common carotid artery was measured continuously with an echo-tracking device with the rats under anesthesia with halothane. Intra-arterial pressure was monitored on the contralateral side. L-NAME rats exhibited arterial pressures similar to those of SHR. The distensibility pressure-curve determined in L-NAME rats was a direct continuation of that obtained in control rats. In contrast the distensibility in SHR was increased (P < .01, SHR versus L-NAME rats). Carotid artery cross-sectional area and left ventricular weight index were increased similarly in SHR and L-NAME rats compared with control rats. Thus the hypertension caused by long-term nitric oxide synthesis inhibition was not associated with the increased arterial distensibility observed in SHR despite similar blood pressure elevations, similar arterial hypertrophy, and consequently similar wall stress. This suggests a role for nitric oxide in regulating the mechanical behavior of arteries exposed to high blood pressure.

Amino Acid Oxidoreductases↗
PubMed1994

Systematic difference between blood pressure readings caused by cuff type.

In this study we determine whether blood pressure readings using a cuff of fixed size systematically differed from readings made with a triple-bladder cuff (Tricuff) that automatically adjusts bladder width to arm circumference and assessed subsequent clinical and epidemiological effects. Blood pressure was measured with a standard cuff or a Tricuff in 454 patients visiting an outpatient clinic in the Seychelles (Indian Ocean). Overall means of within-individual standard cuff-Tricuff differences in systolic and diastolic blood pressures were examined in relation to arm circumference and sex. The standard cuff-Tricuff difference in systolic and diastolic blood pressures increased monotonically with circumference (from 4.7 +/- 0.8/3.2 +/- 0.7 mm Hg for arm circumference of 30 to 31 cm to 10.0 +/- 1.1/8.0 +/- 0.9 mm Hg for arm circumference > or = 36 cm) and was larger in women than men. Multivariate linear regression indicated independent effects of arm circumference and sex. Forty percent of subjects with a diastolic blood pressure of > or = 95 mm Hg measured with a standard cuff had values less than 95 mm Hg measured with a Tricuff. Extrapolation to the entire population of the Seychelles decreased the prevalence of blood pressure greater than or equal to 160/95 mm Hg by 11.5% and 24.0% in men and women, respectively, aged 35 to 64 years. The age-adjusted effect of body mass index on systolic and diastolic blood pressures decreased twofold using blood pressure readings made with a Tricuff instead of a standard cuff.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Clinical utility of ambulatory blood pressure monitoring in the evaluation of patients with borderline hypertension.

Blood pressure measured in the physician's office often differ considerably from those recorded during everyday activities away from the medical environment. This fact is particularly important in patients whose office blood pressures are only mildly elevated because, in a large proportion of these people, the elevation is observed only when blood pressures are measured in the physician's office and not when they are measured during normal activities. There is little evidence that this 'white-coat' hypertension is associated with increased cardiovascular risk, but patients with the condition are prone to develop sustained hypertension over time. It is therefore advisable to monitor these individual regularly so that antihypertensive therapy can be initiated when appropriate.

Antihypertensive Agents↗
PubMed1994

Angiotensin-II mediates norepinephrine and neuropeptide-Y secretion in a human pheochromocytoma.

The potential role of angiotensin-II in mediating catecholamine and neuropeptide-Y release in a human pheochromocytoma has been investigated. Angiotensin-II type I receptors are transcribed and translated into functional proteins in a surgically removed pheochromocytoma. Primary cell culture of the tumor has been studied in a perfused system. Angiotensin-II increased the release of norepinephrine and neuropeptide-Y by the pheochromocytes. Activation of the angiotensin-II type I receptors by angiotensin-II was associated with a rise in cytosolic free calcium. The renin-angiotensin system may, therefore, contribute to the secretion of catecholamines and NPY occurring in patients with pheochromocytoma and when stimulated trigger hypertensive crisis.

Adrenal Gland Neoplasms↗
PubMed1994

Use of drugs with more than a twenty-four-hour duration of action.

AIM: To assess compliance with a drug regimen of two doses a day compared with one a day. PATIENTS AND METHODS: A prospective crossover study was set up in a general practice environment to compare compliance on a drug regimen of once a day versus twice a day. Data were collected by electronic monitoring in 113 patients with hypertension or angina pectoris. All patients were prescribed slow-release nifedipine twice a day during the first month and then crossed to a single daily dose of amlodipine for another month. RESULTS: Compliance, defined as the proportion of days on which the correct dose was taken, improved in 30% of patients (95% confidence interval 19-41%; P < 0.001) when the patients were switched from twice a day to once a day, but at the same time there was a 15% increase (95% confidence interval 5-25%; P < 0.02) in the number of patients with one or more no-dose days. Approximately 8% of patients displayed low compliance, irrespective of the dose regimen. Actual dose intervals were used to estimate the extent and timing of periods with unsatisfactory drug activity for various hypothetical drug durations of action. CONCLUSIONS: The apparent advantage of a single daily dose in terms of compliance appears to be clinically meaningful only when the duration of activity extends beyond the dose interval in all patients.

Aged↗
PubMed1994

Angiotensin II antagonists DuP 753 and TCV 116.

BACKGROUND: 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 haemodynamics in some patients with congestive heart failure. It is now possible to chronically antagonize angiotensin II at its receptor using non-peptide angiotensin II inhibitors such as losartan (DuP 753/MK-954) or TCV 116. EFFECT OF NON-PEPTIDE ANGIOTENSIN II ANTAGONISTS: When administered by mouth, DuP 753 and TCV 116 induce dose-dependent inhibition of the pressor response to exogenous angiotensin II. This effect is closely related to circulating levels of the corresponding active metabolites E3174 and CV11974. Preliminary studies performed in hypertensive patients suggest that losartan lowers blood pressure to an equivalent extent to an angiotensin converting enzyme (ACE) inhibitor. CONCLUSIONS: Further investigation is required to show whether these new angiotensin II antagonists compounds compare favourably with ACE inhibitors.

Administration, Oral↗
PubMed1994

The advantages of angiotensin II antagonism.

New approaches to renin-angiotensin blockade: The successful use of angiotensin converting enzyme (ACE) inhibitors in the treatment of hypertension and congestive heart failure has generated a great deal of research interest in developing new pharmacological approaches to block the renin-angiotensin system. In recent years, several new non-peptide angiotensin II antagonists have been synthesized and some of them are available for experimental and/or clinical investigations. Now that experience with the antagonist losartan is accumulating, it is important to compare the effects, the efficacy and the side effects of this agent with those of ACE inhibitors. Effects of losartan compared with ACE inhibitors: So far, ACE inhibitors and the angiotensin II antagonist losartan appear to have similar systemic and regional hemodynamic effects. The impact of ACE inhibition and angiotensin blockade on the various components of the renin-angiotensin system is also comparable except for a marked increase in plasma angiotensin II levels during angiotensin II blockade. This increase in circulating angiotensin II might theoretically lead to an excessive stimulation of the AT2 receptor subtype, but since the function of this receptor is not known it is impossible to evaluate the implications of this reactive rise. Renal effects of losartan: The renal effects of angiotensin II antagonists are also very similar to those of ACE inhibitors. However, a marked increase in uric acid excretion has been observed with the administration of losartan. This uricosuric effect of losartan might represent a clinical advantage unless a state of urinary supersaturation of undissociated uric acid is achieved.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1993

[The importance of therapy compliance in the treatment of arterial hypertension].

The hypertensive patient remains mostly asymptomatic and requires medication over his entire life. A sufficient follow-up may sometimes be difficult. Poor control of blood pressure is frequently due to inadequate compliance with the prescribed medication. This compliance is therefore a factor to be considered in any instance of a follow-up consultation of a hypertensive patient.

Antihypertensive Agents↗
PubMed1993

[Blood pressure recording in outpatient service: experience with the Sandoz Pressure System].

The Sandoz Pressure System (SPS) is a widely used device for ambulatory blood pressure recording. The accuracy of blood pressure profiles recorded in daily routine with this device has been demonstrated. In 34 untreated hypertensive patients the blood pressure values were in good agreement with measurements taken by auscultation. The variability of recordings was less or equal to 5 mmHg in 10% of patients for the systolic and in 94% of patients for the diastolic value. During daily activity 100 +/- 6% (mean +/- standard deviation) of the values expected by programming were available for analysis. These results confirm that arterial pressure under ambulatory conditions cannot be reliably predicted based on blood pressure measurements in the doctor's office.

Adult↗
PubMed1993

High level expression of human neuropeptide Y receptors in mammalian cells infected with a recombinant vaccinia virus.

Neuropeptide Y (NPY) is a 36 amino acid peptide present in the central and peripheral nervous system. Numerous studies point to a role of NPY in cardiovascular regulation. NPY effects are mediated through stimulation of specific cell surface G protein-coupled receptors. To allow biochemical studies of the receptor and of its interaction with the ligand, we have developed a potent expression system for NPY receptors using a recombinant vaccinia virus. A human NPY receptor cDNA was fused to a strong vaccinia virus promoter and inserted into the viral genome by homologous recombination. Recombinant viruses were isolated and tested for their ability to induce NPY binding site expression following infection of mammalian cell lines. Using saturation and competition binding experiments we measured a Bmax of 5-10 x 10(6) NPY binding sites per cell. The Kd for the binding of NPY is about 20 nM. Labelling of infected cells with a fluorochrome-labelled NPY indicated that the recombinant protein integrates into the cell membrane.

Base Sequence↗
PubMed1993

Elastic behaviour of the carotid artery in intact spontaneously hypertensive rats.

Intact spontaneously hypertensive rats (SHR) were studied to assess the effect of prolonged antihypertensive treatment on the elastic behaviour of the external carotid artery. Thirty-week-old SHR received the ACE inhibitor captopril, the arteriolar dilator hydralazine or their vehicle for 6 weeks. These rats were compared to normotensive, vehicle treated WKY rats. The internal diameter of the carotid artery was measured continuously in halothane-anaesthetized rats using an echo-tracking device, and intra-arterial pressure was also monitored continuously, on the contralateral side. Captopril- and hydralazine-treated SHR as well as normotensive controls had similar blood pressure values. No significant shift in the distensibility-pressure curves was observed among vehicle-treated SHR and WKY rats or the SHR which had received captopril or hydralazine. Histological examination of the carotid artery fixed ex vivo with paraformaldehyde showed a significant increase in cross-sectional area in vehicle-treated SHR as compared to their normotensive counterparts. These results therefore suggest that the elastic behaviour of elastic arteries is not necessarily altered by the structural changes developing in response to hypertension.

Animals↗
PubMed1993

Isobaric compliance of the radial artery is increased in patients with essential hypertension.

OBJECTIVES: Hypertension is known to decrease arterial elasticity and systemic compliance. However, the arterial tree is not a homogeneous system, and whether a distal medium-sized artery such as the radial artery behaves like proximal arteries has not been determined. The aims of the present study were, first, to characterize non-invasively the mechanical properties of the radial artery through the determination of the pressure-diameter curve, the distensibility-pressure curve and the compliance-pressure curve, and, secondly, to compare untreated hypertensive patients with normotensive subjects. METHODS: A new high-precision echo-tracking device was developed which allows the diameter of peripheral arteries to be measured continuously. By relating the changes in internal diameter (cross-sectional changes) to those in blood pressure, the cross-sectional arterial compliance could be determined. PARTICIPANTS: Seventy-eight untreated mild or moderate essential hypertensive patients aged 24-78 years were compared with 44 normotensive subjects aged 22-81 years. In order to increase the database and provide independent assessments of the variables examined, the cross-sectional study was performed independently using a standardized procedure in three different research centres. RESULTS: The major finding was that diameter, distensibility and compliance of the radial artery of hypertensive patients were not significantly different from those of normotensive controls when the two populations were studied at their mean arterial pressure. Furthermore, when the two populations were compared for the same level of blood pressure, using distensibility--and compliance--pressure curves, it was clear that isobaric distensibility and compliance of hypertensives were not significantly lower than those of normotensives, being either unchanged or higher. CONCLUSIONS: These findings are in contrast with the well-known decrease in compliance of proximal large arteries due to hypertension. Whether such a difference between proximal large arteries and distal medium-sized arteries may be related to the structural vascular changes observed with long-standing hypertension is still difficult to analyse in humans, and requires further investigation.

Adult↗
PubMed1993

Efficacy and safety of various combination therapies based on a calcium antagonist in essential hypertension: results of a placebo-controlled randomized trial.

We tested the efficacy and safety of different combination therapies in hypertensive patients with uncontrolled blood pressure (BP) on a monotherapy with a calcium antagonist: 1,647 hypertensive patients were enrolled to receive placebo for 4 weeks followed by isradipine (ISR) 2.5 mg twice daily (b.i.d.) for 4 weeks. Nonresponders [diastolic BP (DBP) > 90 mm Hg] were randomly assigned to receive either the beta-blocker bopindolol 0.5 or 1 mg/day, the diuretic metolazone 1.25 or 2.5 mg/day, the angiotensin-converting enzyme (ACE) inhibitor enalapril 10 or 20 mg/day, ISR 5 mg b.i.d., or placebo. One hundred seventy-five receiving placebo dropped out; 93% (n = 1,376) of the 1,472 patients finished 4-week monotherapy with ISR. Sixty percent (n = 826) reached target BP, and 40% (n = 550) remained uncontrolled and were randomized. Regardless of dosage, all drugs led to a comparable reduction in BP except for the lower dosage of bopindolol and ISR 5 mg b.i.d., which were less effective in lowering systolic BP (SBP). The BP decrease achieved by combination therapy ranged from 10 to 15 mm Hg SBP and from 7 to 11 mm Hg DBP but remained unchanged with placebo. Side effects were minor, and only 2.4% of patients discontinued therapy because of side effects. The side-effect score for edema was lower with ISR plus diuretics than with other combinations, whereas the ACE inhibitor was associated with a higher score for cough. Monotherapy with a calcium antagonist normalizes BP in about two-thirds of patients when used in general practice.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗