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Biomedical subjects

B Waeber

Publications and source records attributed to B Waeber.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Production and characterization of four anti-neuropeptide Y monoclonal antibodies.

Human neuropeptide Y (hNPY) is a potent vasoconstrictor peptide of 36 aminoacid residues. We isolated hybridomas secreting four monoclonal antibodies directed against various epitopes of neuropeptide Y and studied their cross-reactivity with peptide YY (PYY) and the pancreatic polypeptide (PP), two peptides sharing sequence homologies with hNPY (respectively 70% and 50%). The antibody NPY02 is an IgG1 with a Ka of 5.5 x 10(10) liters/mol. It binds to the 11-24 region of NPY (IC50 = 2 x 10(-7)M), does not recognize PP but cross-reacts weakly with PYY. Antibodies NPY03 and NPY05 are IgG2 with respective Ka's of 6.7 x 10(9) and 2.5 x 10(10) liters/mol. They interact with a C-terminal epitope on NPY (NPY 27-34, IC50 = 2 x 10(-9) M for NPY03 and NPY 32-36, IC50 = 1 x 10(-9) M for NPY05). These two antibodies cross-react with PYY whereas only NPY05 binds PP. NPY05 is unable to bind the free acid form of neuropeptide Y. The 32-36 COOH free subpeptide is recognized 50,000 less efficiently by NPY05 than its amidated form. Antibody NPY04 is an IgG3 with a Ka of 3.8 x 10(8) liters/mol. It recognizes a N-terminal epitope between aminoacids 1 and 12 (IC50 = 2.5 x 10(-6) M). NPY04 interacts weakly with PYY but not detectably with PP. These results obtained with 4 different monoclonal antibodies demonstrate the presence of at least four epitopes on hNPY, two of them being continuous. These antibodies will be used to study the interaction of NPY with its receptor and to develop sensitive and specific assays for determination of NPY concentrations in biological fluids.

Amino Acid Sequence↗
PubMed1992

Clinical experience with angiotensin II receptor antagonists.

This series of studies was designed to assess in normal volunteers the relationships between various doses (5, 10, 20, 40, 80, and 120 mg) of the orally active angiotensin II antagonist losartan (DuP 753, MK-954) and their inhibitory effect on the pressure response to a given bolus of angiotensin I or II. It was found that the maximal inhibitory effect was reached with a dose of 80 mg. The minimal dose necessary for maximal efficacy would therefore be expected to be between 40 and 80 mg. The effect lasted for more than 24 h and was related almost exclusively to the circulating levels of the active metabolite EXP3174. It remains to be demonstrated in hypertensive patients that the same dose relationship holds for the antihypertensive effect, but preliminary data already suggest that this is the case.

Administration, Oral↗
PubMed1992

Inhibitory effect of neuropeptide Y on stimulated renin secretion of awake rats.

1. (1-36)-NPY is a vasoconstrictor peptide widely distributed in sympathetic nerve terminals. This peptide exerts an inhibitory action on renin release induced by various stimuli. Post-synaptic neuropeptide Y (NPY) receptors show a high affinity for (1-36)-NPY as well as for the agonist (Pro34)-NPY, while presynaptic receptors bind preferentially (13-36)-NPY. 2. This study was undertaken to assess whether the NPY induced renin suppression in awake normotensive rats infused with the beta-adrenoceptor stimulant isoproterenol is mediated by activation of pre- or post-synaptic receptors. 3. Non-pressor doses of (1-36)-NPY and (Pro34)-NPY markedly attenuated the renin secretion triggered by isoproterenol whereas (13-36)-NPY had no effect. This suggests that the effect of NPY on renin release is due to the stimulation of post-synaptic receptors. However it remains unknown whether NPY acts directly on juxtaglomerular cells or indirectly by modifying intraglomerular haemodynamics.

Animals↗
PubMed1992

Amlodipine compared to nitrendipine in hypertensive patients: the effects on toleration in relationship to the onset of action.

Amlodipine and nitrendipine are calcium antagonists of the 1,4-dihydropyridine group which differ in their pharmacokinetic and pharmacodynamic properties. The clinical relevance of these differences was investigated in a study designed to compare the efficacy and safety of once-daily amlodipine (5 mg) and nitrendipine (20 mg) in patients with mild-to-moderate essential hypertension. Ambulatory blood pressure monitoring and conventional measurements showed that amlodipine and nitrendipine produced comparable reductions in blood pressure after 4 weeks of treatment. However, the onset of the antihypertensive effect was gradual for amlodipine, while most of the reduction achieved at the end of treatment with nitrendipine was seen after the first dose. There were no significant changes in heart rate with amlodipine, but significant increases occurred during the first 6 h of nitrendipine treatment. Amlodipine was associated with a significantly lower incidence of vasodilator-related adverse effects at initiation of therapy (headache, flushing, tachycardia) compared with nitrendipine, which may reflect its slower onset of action. The different pharmacodynamic and toleration profiles of amlodipine and nitrendipine at therapeutically equivalent doses suggest that amlodipine may have advantages in the treatment of hypertension, especially in terms of the low incidence of acute side effects, which may ultimately translate into improved patient compliance.

Adult↗
PubMed1992

Ambulatory blood pressure monitoring as a means to avoid overtreatment of elderly hypertensive patients.

Do elderly similarly to younger hypertensive patients tend to be overtreated if therapeutic decisions are based exclusively on blood pressure measured by the physician in his office? Eighteen hypertensive patients (10 previously treated) aged 70 years or more had repeatedly office systolic blood pressure greater than or equal to 170 mm Hg and/or diastolic blood pressure greater than or equal to 100 mm Hg. The physicians in charge were asked to reduce blood pressure within 4 months to a target of less than or equal to 160/95 mm Hg using any drug regimen. Blood pressure was monitored during daytime using a noninvasive blood pressure recorder, but the results of the recording were not available to the physicians until the end of the study. At the outset, 11 patients had a mean ambulatory recorded blood pressure less than 170/100 mm Hg. Those patients who exhibited high blood pressures only in the doctor's presence did not reduce their ambulatory blood pressure when antihypertensive therapy was initiated or intensified in order to reduce office blood pressure. This contrasted with the significant fall in ambulatory blood pressure observed in the presence of the doctor. Thus ambulatory blood pressure monitoring seems useful to avoid overtreatment not only of younger but also of elderly hypertensive patients.

Aged↗
PubMed1992

Conduit artery compliance and distensibility are not necessarily reduced in hypertension.

The goal of this study was to investigate whether the elastic behavior of conduit arteries of humans or rats is altered as a result of concomitant hypertension. Forearm arterial cross-sectional compliance-pressure curves were determined noninvasively by means of a high precision ultrasonic echo-tracking device coupled to a photoplethysmograph (Finapres system) allowing simultaneous arterial diameter and finger blood pressure monitoring. Seventeen newly diagnosed hypertensive patients with a humeral blood pressure of 163/103 +/- 4.4/2.2 mm Hg (mean +/- SEM) and 17 age- and sex-matched normotensive controls with a humeral blood pressure of 121/77 +/- 3.2/1.9 mm Hg were included in the study. Compliance-pressure curves were also established at the carotid artery of 16-week-old anesthetized spontaneously hypertensive rats (n = 14) as well as Wistar-Kyoto normotensive animals (n = 15) using the same echo-tracking device. In these animals, intra-arterial pressure was monitored in the contralateral carotid artery. Mean blood pressures averaged 197 +/- 4 and 140 +/- 3 mm Hg in the hypertensive and normotensive rats, respectively. Despite the considerable differences in blood pressure, the diameter-pressure and cross-sectional compliance-pressure and distensibility-pressure curves were not different when hypertensive patients or animals were compared with their respective controls. These results suggest that the elastic behavior of a medium size muscular artery (radial) in humans and of an elastic artery (carotid) in rats is not necessarily altered by an increase in blood pressure.

Animals↗
PubMed1992

Non-invasive determination of arterial diameter and distensibility by echo-tracking techniques in hypertension.

METHODOLOGY: A new non-invasive ultrasonic device was developed to characterize the biomechanical properties of medium and large peripheral arteries. Simultaneous recordings of internal diameter and blood pressure over the whole cardiac cycle are used to establish compliance-pressure curves. Since blood pressure, which is an inherent co-determinant of arterial compliance, is taken into account, the comparison of arteries from patients with markedly different blood pressures has become possible. In a first study, the effects of three different antihypertensive drugs (20 mg lisinopril, 100 mg atenolol, 20 mg nitrendipine administered once a day) on arterial compliance and distensibility were investigated in young healthy volunteers. RESULTS: After 8 days of treatment, lisinopril induced a significant increase in arterial compliance. Subsequently, we compared the mechanical behaviour of arteries from newly diagnosed hypertensive patients (radial artery) or the carotid artery from spontaneously hypertensive rats (SHR) with that of corresponding arteries in normotensive counterparts. No decrease in arterial distensibility was found in the hypertensive groups over the measured blood pressure range. This result is not totally consistent with previous in vitro or in situ localized studies. Methodological differences, the absence of blood flow and/or denervation may partly explain these contradictory results. Finally, we tested the effects of hydralazine (5 mg/day) and captopril (25 mg/day), administered for 6 weeks in drinking water, on the behaviour of the carotid arteries of 16-week-old SHR. The two drugs effectively reduced blood pressure while shifting the distensibility-pressure curves upward in comparison to the placebo-treated animals, suggesting an improvement in arterial compliance. CONCLUSIONS: While hypertension does not itself appear to alter the elastic behaviour of large peripheral arteries, antihypertensive treatment may increase the compliance of these blood vessels.

Adult↗
PubMed1992

Conclusions on the measurement of arterial wall thickness: anatomic, physiologic and methodologic considerations.

AIM: To discuss the use of new ultrasonic techniques that make it possible to visualize elastic (carotid) and muscular (radial) capacitance arteries non-invasively. RESULTS OF DATA REVIEW: Measurements of carotid wall thickness and the detection of atheromas are related to arterial pressure, to other risk factors and to the risk of subsequent complications. The use of high-frequency ultrasound (7.5-10 MHz), measurements of far wall thicknesses in areas free of atheromas at end-diastole (by ECG gating or pressure waveform recording) and descriptions of the size and characteristics of atherosclerotic plaques allow a non-invasive assessment of vascular hypertrophy and atherosclerosis in hypertensive patients. CONCLUSIONS: Careful attention to methodologic and physiologic factors is needed to provide accurate information about the anatomy of the dynamically pulsating arterial tree.

Arteries↗
PubMed1992

Effect of mental stress on the tone of a medium-sized muscular artery.

AIM: We studied the effects of mental stress on the tone of the radial artery, a medium-sized muscular artery. METHODS: Using an A-mode echo-tracking device coupled to a photoplethysmograph, we took continuous measurements of the radial artery diameter, heart rate and finger arterial pressure in six healthy young volunteers. RESULTS: Under mental stress, the heart rate increased from 63 +/- 4 to 74 +/- 4 beats/min (mean +/- SEM, P < 0.01) and systolic pressure from 123 +/- 5 to 140 +/- 6 mmHg (P < 0.05). No consistent modification in the arterial diameter was observed at this time. CONCLUSION: The activation of sympathetic nerve activity induced by mental stress does not cause a significant contraction in the radial artery.

Adolescent↗