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Biomedical subjects

B Waeber

Publications and source records attributed to B Waeber.

At least 73 records · Page 4Linked to original sources
PubMed1998

Vasopressin dilates the rat carotid artery by stimulating V1 receptors.

The acute effects of various vasopressor agents on the diameter of the common carotid artery were studied in halothane-anesthetized normotensive rats. The animals were infused intravenously for 60 min with equipressor doses of angiotensin II (10 ng/min), the alpha1-stimulant methoxamine (5 microg/min), lysine vasopressin (5 mU/min), or vehicle. The arterial diameter was measured by using a high-resolution ultrasonic echo-tracking device. The three vasoconstrictors increased the carotid artery diameter, but this effect was significantly more pronounced with lysine vasopressin. Even a nonpressor dose of lysine vasopressin (1 mU/min) caused a significant increase in the arterial diameter. The lysine vasopressin-induced vasodilatation could be prevented by the administration of d(CH2)5Tyr(Me)AVP (10 microg, i.v.), a selective V1-vasopressinergic receptor antagonist. These data therefore suggest that a short-term increase in blood pressure induces in rats a distention of the carotid artery. The increase in arterial diameter seems to involve an active mechanism with lysine vasopressin caused by the stimulation of V1-vasopressinergic receptors.

Angiotensin II↗
PubMed1998

Potential cardioprotective effect of mibefradil in the long-term treatment of hypertension.

During the last 2 decades, remarkable progress has been made in the treatment of hypertension with the discovery of new drugs lowering blood pressure by various mechanisms, e.g. calcium channel blockers, angiotensin-converting enzyme inhibitors and angiotensin II antagonists. These antihypertensive agents are now widely used as first-line therapy although there is still no definite proof that they have a cardioprotective effect and reduce the mortality rate in patients with coronary heart disease. Mibefradil is a new calcium antagonist with a novel mechanism of action since it is the only drug available so far able to block T channels. This compound might be particularly effective in preventing cardiac morbidity and mortality. It reduces heart rate when lowering blood pressure, has no negative inotropic effect, allows regression of cardiac hypertrophy and is effective in the treatment of angina. Mibefradil produces a sustained blood pressure reduction with a close to optimal trough:peak ratio. A major advantage of this novel compound is its excellent tolerability over the dose range recommended (50-100 mg/day). In particular, leg edema is seen clearly less often during mibefradil treatment than during therapy with dihydropyridines. Mibefradil has therefore an attractive profile in terms of both efficacy and safety and represents a promising first-line option to treat hypertensive patients.

Benzimidazoles↗
PubMed1998

Knowledge, attitudes, and practices on hypertension in a country in epidemiological transition.

Assessment of knowledge, attitudes, and practices (KAP) is a crucial element of hypertension control, but little information is available from developing countries where hypertension has lately been recognized as a major health problem. Therefore, we examined KAP on hypertension in a random sample of 1067 adults aged 25 to 64 years from the Seychelles Islands (Indian Ocean). KAP were assessed from an administered structured questionnaire. The age-standardized prevalence of hypertension (screening blood pressure [BP] > or = 160/95 mm Hg or taking antihypertensive medication) was 36% in men and 25% in women aged 25 to 64 years. Among hypertensive persons, 50% were aware of the condition, 34% were treated, and 10% had controlled BP (ie, BP <160/95 mm Hg). Most persons, whether nonhypertensive, unaware hypertensive, or aware hypertensive, had good basic knowledge related to hypertension determinants and consequences, possibly an effect of a nationwide cardiovascular disease prevention program over the last years. However, favorable outcome expectation, positive attitudes, and appropriate practices for hypertension and relevant healthy lifestyles were found in smaller proportions of participants, with little difference between aware hypertensives, unaware hypertensives, and nonhypertensives. Furthermore, hypertensive persons with other concurrent cardiovascular risk factors affecting the overall heart risk knew well the detrimental effects of these other factors but reported making little actual change to control them (particularly regarding overweight and sedentary habits). These data point to the need to maximize the efficiency of hypertension prevention and control programs so that delay in achieving effective hypertension control is minimized in countries experiencing recent emergence of hypertension as a major public health problem.

Adult↗
PubMed1998

A look through the new therapeutic window: irbesartan.

Although an impressive array of efficacious antihypertensive agents are available to treat hypertension, the optimal use of these agents is limited by dose-related side-effect profiles. This is particularly the case for widely used first-line antihypertensive agents such as diuretics, beta-blockers, calcium antagonists, and alpha1-blockers; this represents a major therapeutic dilemma in treating hypertension. With the development of the angiotensin II receptor antagonists (AIIRAs), this dilemma might have been solved. Irbesartan is a long-acting AIIRA that provides dose-related efficacy with placebo-like tolerability at all clinical doses. The results of placebo and active-control trials of irbesartan have demonstrated that the agent is as effective as the leading members of major antihypertensive classes with respect to blood pressure control, while having superior tolerability. Pooled data from nine multicenter, randomized, placebo-controlled trials with irbesartan have documented no adverse events caused by dose-response. This feature could widen the traditionally narrow therapeutic window in the treatment of hypertension and point to the use of AIIRAs such as irbesartan as first-line therapy in the management of hypertension.

Angiotensin Receptor Antagonists↗
PubMed1997

Hypertension increases connexin43 in a tissue-specific manner.

BACKGROUND: Connexin43 (Cx43), a membrane protein involved in the control of cell-to-cell communication, is thought to play a role in the contractility of the vascular wall and in the electrical coupling of cardiac myocytes. The aim of this study was to investigate the effects of experimental hypertension on Cx43 expression in rat aorta and heart. METHODS AND RESULTS: Rats were made hypertensive after one renal artery was clipped (two kidney, one-clip renal model) or after the administration of deoxycorticosterone and salt (DOCA-salt model). After 4 weeks, all rats showed a similar increase in intra-arterial mean blood pressure and in the thickness of both the aortic wall and the heart. Northern blot analysis of aorta mRNA and immunolabeling for Cx43 showed that hypertensive rats expressed twice as much Cx43 in aorta as the control animals. In contrast, no difference in Cx43 mRNA or in the immunolabeled protein was observed in heart. CONCLUSIONS: The results show that rats exhibiting a similar degree of blood pressure elevation, as the result of different mechanisms, feature a comparable increase in Cx43 gene expression, which was observed in the aortic but not in the cardiac muscle. These data suggest that localized mechanical forces induced by hypertension are major tissue-specific regulators of Cx43 expression.

Animals↗
PubMed1997

Relationship between the prescriber's instructions and compliance with antibiotherapy in outpatients treated for an acute infectious disease.

Antibiotics are frequently prescribed in everyday practice for the management of acute microbial infections. The present study was designed to assess the relationship between the prescriber's instructions and the patient's adherence to a prescribed schedule of twice-daily doses of antibiotic for at least 5 days to treat an infectious disease. The trial was conducted by ten practicing physicians on ambulatory patients. Compliance with the antibiotic regimen was evaluated using a microelectronic device, the Medication Event Monitoring System (MEMS). Seventy patients were prescribed an antibiotic in twice-daily doses for 5 to 14 days (mean = 8). Data were available for analysis from 68 of them, aged 18 to 84 years (mean = 44). The "taking compliance" for the whole story group, which corresponded to the ratio of the number of times the bottle was opened and the total number of doses prescribed during the monitoring period, was nearly perfect at 99.6%. However, only 32.6% of the medications was taken within 1 hour before or after the 12-hour interval expected to be optimal for a twice-daily regimen. It therefore seems highly desirable that physicians give more detailed recommendations to their patients regarding the drug regimens they prescribe.

Adolescent↗
PubMed1997

Hypertension differentially affects the expression of the gap junction protein connexin43 in cardiac myocytes and aortic smooth muscle cells.

Electrical and mechanical coupling of myocytes in heart and of smooth muscle cells in the aortic wall is thought to be mediated by intercellular channels aggregated at gap junctions. Connexin43 (Cx43) is one of the predominant membrane proteins forming junctional channels in the cardiovascular system. This study was undertaken to assess its expression during experimental hypertension. Rats were made hypertensive by clipping one renal artery (two-kidney, one-clip renal hypertension) or by administering deoxycorticosterone and salt (DOCA-salt hypertension). After four weeks, rats from both models showed a similar increase in intra-arterial mean blood pressure, as well as in the thickness of both aorta and heart walls. Northern blot analysis showed that, compared to controls, hypertensive rats expressed twice more Cx43 in aorta, but not in heart. These results suggest that localized mechanical forces induced by hypertension are major tissue-specific regulators of Cx43 expression.

Animals↗
PubMed1997

Combination antihypertensive therapy: does it have a role in rational therapy?

The pharmacological treatment of hypertension allows one to reduce substantially the risk of developing a cardiovascular complication. It appears more and more important to bring blood pressure to normal values in order to get the maximal benefit from antihypertensive therapy. Blood pressure lowering drugs make it possible to control blood pressure in about half of the patients when administered as monotherapy. The fraction of patients with a normal blood pressure can be markedly increased by combining drugs acting by different mechanisms. Low doses of antihypertensive agents are generally enough when coadministered. This helps to keep the incidence of side effects minimal and facilitates the patient's compliance with long-term treatment. Low-dose, fixed-dose combination therapy may therefore represent a valuable option not only to treat hypertensive patients unresponsive to drugs given as monotherapy, but also to initiate the treatment.

Antihypertensive Agents↗
PubMed1997

SC-52458, an orally active angiotensin II-receptor antagonist: inhibition of blood pressure response to angiotensin II challenges and pharmacokinetics in normal volunteers.

This study was designed to assess in normal volunteers the potency, efficacy, and tolerability of the new nonpeptidic, orally active, angiotensin (Ang) II subtype 1 (AT1)-receptor antagonist SC-52458. After a randomized, single-blind, placebo-controlled protocol, two groups of eight healthy men ingested placebo or increasing single oral doses (10, 25, and 50 mg or 100, 150, and 200 mg) of SC-52458. Finger blood pressure (BP) was continuously monitored (Finapres), and BP response to repeated intravenous challenges with Ang II was compared with baseline BP response to the same dose of Ang II. Up to 24 h after drug intake, effects on plasma renin activity (PRA), Ang II, and aldosterone and pharmacokinetics were estimated. One, 4, and 10 h after the 200-mg dose, diastolic BP response to Ang II challenges was decreased from 30.3 to 2.6 mm Hg (mean +/- SEM; n = 8; i.e., to 8.3 +/- 1.1% of baseline response), 10.1 mm Hg (35.4 +/- 1.8%), and 17.5 mm Hg (58.7 +/- 1.8%), respectively. SC-52458 produced dose-related increases in PRA and Ang II concentrations < or = 10 h after drug intake. Plasma aldosterone concentrations tended to be decreased for < or = 24 h after SC-52458 doses of > or = 100 mg. No drug-related side effects were observed. The pharmacokinetics were linear over the dose range of 10-150 mg (t1/2 = 1.14-2.39 h). Efficacy was dose dependent, with a peak effect after 1 h. In conclusion, the novel AT1-receptor antagonist SC-52458 is well tolerated and orally active. It produces a rapid-onset inhibition of the renin-angiotensin system and reduces BP response to Ang II for > or = 10 h. These characteristics promise strong antihypertensive properties for SC-52458.

Administration, Oral↗
PubMed1997

Low-dose combinations versus monotherapies in the treatment of hypertension.

RATIONALE FOR DRUG COMBINATIONS: Essential hypertension is a heterogeneous disease. Different factors might interact, in an individual patient, to increase blood pressure. This explains why a drug that lowers blood pressure by a given mechanism may normalize blood pressure in some patients but not in others. combining two drugs with complementary mechanisms of action can increase the antihypertensive efficacy. DOSAGES USED IN DRUG COMBINATIONS: When administered in combination, lower doses of the separate components are generally necessary than when the drugs are prescribed as monotherapies, which may improve tolerability. Fixed-dose combination therapy is therefore an attractive approach to the treatment of hypertensive patients. It may be an appropriate choice, not only for second-line, but also for first-line therapy.

Antihypertensive Agents↗
PubMed1997

[Measurement of blood pressure: best way to assess cardiovascular risk?].

Measurement of the blood pressure by the physician remains an essential step in the evaluation of cardiovascular risk. Ambulatory measurement and self-measurement of blood pressure are ways of counteracting the "white coat" effect which is the rise in blood pressure many patients experience in the presence of doctors. Thus, it is possible to define the cardiovascular risk of hypertension and identify the patients with the greatest chance of benefiting from antihypertensive therapy. However, it must be realised that normotensive subjects during their everyday activities and becoming hypertensive in the doctor's surgery, may become hypertensive with time, irrespective of the means used to measure blood pressure. These patients should be followed up regularly even if the decision to treat has been postponed.

Antihypertensive Agents↗
PubMed1996

[Angiotensin II antagonists: a distinct therapeutic class].

Angiotensin II antagonists are a promising new class of antihypertensive agents. Unlike angiotensin converting enzyme inhibitors, these new agents block the renin-angiotensin system by acting directly on the angiotensin II receptor. It is quite probable that these agents will become a first line therapeutic choice for hypertensive patients. Current clinical trials on primary prevention may confirm the indications for this new therapeutic class in a near feature.

Angiotensin II↗
PubMed1996

[Ambulatory blood pressure monitoring in the assessment of the hypertensive patient].

Non-invasive ambulatory blood pressure monitoring allows to record numerous blood pressures during everyday activities. The relationship between blood pressure and target organ damage is closer with ambulatory than conventional office blood pressures. Monitoring blood pressure outside the doctor's office appears more and more useful in diagnosing and treating hypertension. This approach makes it possible to recognize high-risk hypertensive patients, i.e. patients exhibiting abnormally increased blood pressures in the presence as well as in the absence of the doctor.

Antihypertensive Agents↗
PubMed1996

[Diagnosis and treatment of arterial hypertension in the elderly].

The incidence of hypertension increases with age and becomes very high in the seventh decade. The increase of the blood pressure may be systolic, diastolic or both. Various controlled studies have shown that the treatment of hypertension in the elderly reduces the incidence of myocardial infarction and of stroke. It appears today that also patients with isolated systolic hypertension benefit from antihypertensive treatment. All classes of antihypertensive agents, including beta-blocking drugs, may be used in the elderly.

Aged↗
PubMed1996

Albuminuria in diabetes mellitus: relation to ambulatory versus office blood pressure and effects of cilazapril.

This study aimed to investigate the relationship between microalbuminuria and office blood pressure (BP) as compared with ambulatory BP in patients with diabetes mellitus under everyday practice conditions. It was also undertaken to assess the effect of the angiotensin converting enzyme inhibitor cilazapril on diabetes-associated albuminuria. Ambulatory BP was recorded during daytime in 54 patients with type II diabetes mellitus at the end of a 4-week period during which they received no vasoactive drug. The difference between office and ambulatory BP was unpredictable in the individual patient. There was no significant correlation between either ambulatory or office BP and urinary albumin/p5eatinine ratio. Fifty-one patients underwent a 40-week treatment with 5 mg/day of cilazapril. There was, in the absence of satisfactory BP control, the possibility of adding the calcium antagonist amlodipine (5 mg/day) from the 10th week onward and 12.5 mg/day of hydrochlorothiazide from the 20th week onward. Office mean BP was significantly reduced after 30 to 40 weeks of therapy in patients with normoalbuminuria (n = 19, -14%, P < .001), in those with microalbuminuria (n = 22, -6.6%, P < .01), as well as in those with clinical proteinuria (n = 9, -11.4%, P < .01). During the same time, the urinary albumin/creatinine ratio was not modified in normoalbuminuric patients (n = 19, +24.6%, P = .72) as well as in those with clinical proteinuria (n = 9, -29.4%, P = .09). On the other hand this value was significantly reduced for the group with microalbuminuria (n = 23, -24.3%, P < .05). In the overall population, as well as in hyperalbuminuric patients (patients with microalbuminuria + patients with clinical proteinuria), the reduction of the albumin/ creatinine ratio was also significant (n = 51, -7%, P < .01 and n = 32, -25,7%, P < .01, respectively). In conclusion, the findings of this study performed by practicing physicians show that ambulatory BP may differ greatly from office BP in diabetic patients. They also indicate that urinary albumin excretion is poorly correlated with office and ambulatory BP in type II diabetics. Finally, they demonstrate the antiproteinuric action of prolonged treatment with the angiotensin converting enzyme inhibitor cilazapril, whether given alone or combined with amlodipine.

Adolescent↗
PubMed1996

Isolated office hypertension: a prehypertensive state?

OBJECTIVE AND METHOD: Isolated office hypertension, defined as hypertensive blood pressure values in a medical setting but normal self-measured or ambulatory-recorded blood pressures, is frequently encountered in clinical practice. Yet, whether this condition represents a transient state in the development of a sustained ambulatory hypertension is still unknown as no long-term analysis of the evolution of ambulatory blood pressure has been carried out in patients with isolated office hypertension. To evaluate whether such patients should be considered as truly normotensive or hypertensive, we have studied the long-term changes in office and ambulatory blood pressures in 81 patients in whom isolated office hypertension was observed between 1982 and 1988. RESULTS: After a 5-6 year follow-up, 60 of the 81 patients had a mean 12 h daytime ambulatory blood pressure greater than 140/90 mmHg, suggesting an evolution towards ambulatory hypertension. The development of hypertension could not be predicted on the basis of the follow-up office blood pressures as these tended to decrease during the follow-up period. CONCLUSIONS: The results of this study suggest that patients with isolated office hypertension should not be considered as truly normotensive individuals. Hence, these patients require a careful medical follow-up. Office blood pressure readings alone, however, do not appear to provide a good indicator of the long-term outcome of isolated office hypertension.

Adolescent↗