Study on antihypertensive efficacy of slow-release verapamil: pharmacokinetic and noninvasive hemodynamic profile.
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Biomedical subjects
Publications and source records attributed to V Vulpis.
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The new alpha 1-blocker alfuzosin was compared with propranolol as monotherapy for hypertension in a double-blind, parallel group study of 8-week duration in 40 patients with essential hypertension. The patients (11 males, 29 females; mean age 47.8 +/- 2.2 years in the alfuzosin group and 46.6 +/- 2.4 years in the propranolol group) randomly received either alfuzosin from 2.5 mg b.i.d. up to 10 mg b.i.d. or propranolol from 40 mg b.i.d. up to 160 mg b.i.d. according to an individualized dose-titration schedule. The two groups were comparable with respect to disease history, cardiovascular risk factors, concomitant diseases, previous treatments and end-placebo blood pressure and heart rate values. Four patients did not complete the study, two patients in the alfuzosin group: one patient because of postural hypotension and the second one because of breast cancer; and two patients in the propranolol group: one patient for inefficacy and the second one lost to follow-up. At the end of the 8-week trial the mean daily doses were 12.2 +/- 0.61 mg and 196 +/- 9.82 mg for alfuzosin and propranolol, respectively. The antihypertensive effects of the two drugs were comparable. Upright and supine blood pressures decreased significantly with both treatments from the second week on (P less than 0.001 for all BP values). At the end of the 8-week double-blind trial, 83% of alfuzosin patients and 67% of propranolol patients were normalized. The two treatments differed significantly with respect to their effect on heart rate. Alfuzosin did not induce marked changes in heart rate: only a slight increase was observed. In contrast, propranolol caused bradycardia, more marked in the upright position. Palpitations, headache, asthenia and orthostatic hypotension were reported in the alfuzosin group. Asthenia and decreased libido were reported in the propranolol group. These data prove that alfuzosin has antihypertensive effects equivalent to propranolol and it is an interesting agent for the therapy of essential hypertension. It can be used as a first agent at doses between 5 and 20 mg/day with satisfactory therapeutic response and without relevant side-effects.
Effects of bisoprolol and atenolol on glucose metabolism in hypertensive patients NIDDM. The aim of the study was to compare the antihypertensive efficacy and the effects on glucose metabolism of a new beta 1-selective beta-blocker with high beta 1 selectivity, bisoprolol and atenolol in 12 hypertensive patients (WHO classes I e II) suffering from untreated not insulin-dependent diabetes mellitus (NIDDM). According to a cross-over design after a placebo run-in period of 4 weeks, the patients were randomly allocated to receive bisoprolol 10 mg o.d. or atenolol 100 mg o.d. for 4 weeks, with a four-week wash-out period between the two active treatments. In basal condition and after each therapy an intravenous glucose tolerance test (i.v. GTT, 20 g) was performed, with evaluation of serum glucose and insulin at 0, 15, 30, 60, 90, 120 minutes and glycosuria during the test. At the same time blood pressure, heart rate (supine, upright), ECG, laboratory tests were assessed and subjective tolerability was evaluated. The glucose and insulin responses to the i.v. GTT did not significantly change to basal condition. Similarly glycosuria did not show significative increment during the test with both beta-blocking therapies. Blood pressure and heart rate values were significantly reduced (p less than 0.001) after bisoprolol and atenolol treatment. During the study no side effects were reported and laboratory tests and ECG remained substantially unchanged. These data confirm the antihypertensive efficacy of bisoprolol and atenolol and demonstrate the absence of important effects of these drugs on glucose metabolism in hypertensive patients with NIDDM.
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Heart myosin isoforms and arterial blood pressure changes were studied in 30 SHR rats following a long-term treatment with captopril. 30 Wistar rats were included in the same trial as control. Twelve week old SHR rats with an already established hypertension and ventricular hypertrophy were orally administered with between 25 and 100 mg/Kg/die of captopril. After a ten-week treatment, animals were sacrificed and heart myosin isoforms (V1, V2, V3) analysed by polyacrylamide gel electrophoresis. Our results showed that captopril can: a) reduce blood pressure; b) reduce the cardiac hypertrophy; c) reverse the isomyosin enzymes (V1 V3) previously altered by the hypertrophy condition (V3 V1) to normal value. Furthermore we have detected an increase of V myosin isoform in SHR rats (35%) and to a lower extent in treated Wistar rats (17%). Since SHR and Wistar rats usually do not express V isoform, our results suggest that captopril may be responsible for this phenomenon by acting directly on myocardial cells.
Purpose of this study was to evaluate the long-term effects of treatment by calcium antagonists on blood pressure (BP) and cardiac isomyosins of SHR. From the fourth week of life we studied 40 SHRs and 20 Wistars in standard conditions and at the twelfth week, when SHRs already showed high BP and left ventricular hypertrophy (LVH), we treated 10 of them by nifedipine (N) (30 mg/Kg/die) and 10 by verapamil (V) (100 mg/Kg/die). BP was measured by tail-cuff technique. At the tenth week of treatment when the rats were sacrificed, LVH index and isomyosinic profile were evaluated. The results obtained demonstrate that: at the twenty-second week, V1 was 17% in untreated SHR, 90% in N and 75% in V while V3 was 80% in the untreated group, 8% in N and 15% in V, respectively. In conclusion, the treatment by calcium antagonists reduced BP and LVH re-establishing the predominance of V1 on V3.
In the present study the mechanic activity of SHR and Wistar rat's aorta was evaluated, in vitro, after stimulation by chloride of potassium, phenylephrine, norepinephrine, histamine, serotonin and acetylcholine, before and after the removal of the endothelium. The aorta rings of the rats were taken before the development of the hypertensive state (7th week) and at 18th week (when the SHR rats already showed established hypertension starting since IXth week of life), and successively suspended in a bath for isolated organ. The mechanic activity was measured by isometric transductor. The obtained findings show an increased sensitivity, in SHRs, to (K+), NA and FeE, if these are compared with the control group, since the prehypertensive stage (7th week). The removal of the endothelium didn't modify the response amplitude to K in both the breeds, while the maximum response amplitude, provoked by NA and FeE, significantly increased in SHRs compared to controls. The relaxation induced by the vasodilator agents (Ach-H-5HT) was completely absent in the SHR rats' aorta with established hypertension. In conclusion, these results suggest a functional deterioration of the endothelial cells, in the hypertensive animals, that could contribute to increase the peripheric vascular resistances observed during hypertension.
The aim of this research was to assess left ventricular myosin alterations of Sh, rats during the various phases in which primitive hypertension developed. Two groups of animals were examined: one comprised spontaneously hypertension rats (Shr) and the other controls. Both groups were studied from the 5th to 31st week of life. The Shrs became hypertensive at 9 weeks of age. The animals were sacrificed at: 5-7-9-12-16-24-31 weeks of age. The left ventricles were separated from their hearts and native myosin in non dissociated conditions was then obtained by polyacrylamide gel electrophoresis; heavy chains and light chains were separated with S.D.S. One of the findings showed that in the control rats the myosin iso-enzyme V1 always prevailed over the myosin iso-enzyme V3 during all the stages of life examined. In the Shrs, starting from the iso-enzyme V3 increased proportionally. The heavy chains showed the same behavior as the native protein while there were no significant differences for the light chains in both groups of animals. In conclusion, our findings show that the structural and biochemical compensation variations which several authors have demonstrated in other conditions of experimental hypertension occur in Sh rats as well.
The mechanical reactivity of SHR and Wistar rats' aortas was evaluated, in vitro, after stimulation by potassium chloride (K+), phenylephrine (Phe), norepinephrine (NE), histamine (H), serotonin (5-HT) and acetylcholine (Ach), before and after the removal of the endothelium. The aortic rings were taken at different ages and stages of the hypertensive state (that in the SHRs started at the ninth week of life) and successively suspended in a bath for isolated organs. The mechanical activity was measured by isometric transducers. In SHR rats an increased sensitivity to K+, NE and Phe compared with the control group, and preceding the hypertensive stage, was found. The removal of the endothelium did not modify the response amplitude to K in both the breeds, while the maximum response amplitude, provoked by NE and Phe, significantly increased in SHRs compared to controls. The relaxation induced by vasodilator agents (Ach, H, 5-HT) was significantly reduced in the SHR rats' aortas with initial hypertension (12th week) if compared with Wistar rats at the same age. The release response was completely absent in the SHR rats' aortas with established hypertension (18th week). In conclusion, these results suggest that, in hypertensive rats, a functional deterioration of the endothelial cells occurs: this may contribute to the increase in peripheral vascular resistance observed during hypertension.
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Aim of this study is to investigate the haemodynamic effects, after the short and long-term antihypertensive treatment. After a wash-out period and a placebo treatment period, 30 hypertensive patients received verapamil SR (slow release, 240 mg o.d.) for 30 days. A significant decrease in systolic and diastolic blood pressure was obtained already 4 h after the first administration of verapamil; it was more evident and persistent throughout the study. No significant changes of heart rate or PR interval in ECG were observed. A significant decrease in total vascular resistances, both supine and upright, was evident already 4 h after the drug intake and observed throughout the study. The major effect was obtained after one month. No significant changes of cardiac output, cardiac index and stroke volume were recorded. Furthermore, plasma verapamil levels were measured to confirm that the haemodynamic effects are obtained by low drug concentrations. The present study provides evidence that the antihypertensive effect of verapamil, whose mechanism is the reduction of total vascular resistances, is progressive, long acting and achieved by low plasma levels, when slow release formulation is considered.
To assess the ability of biofeedback (BFB) in controlling hypertension a study was made of 40 hypertensive patients selected by means of the cardiovascular response to an arithmetic test. The patients were divided into four treatment groups: 10 patients were treated with diuretic therapy (D-T), 10 with beta-blocker therapy (Bb-T), 10 with BFB treatment, while 10 had no treatment at all (N-T). The BFB treatment consisted of 36 sittings where patients were requested to control muscular contraction, peripheric temperature and heart rate (HR) by means of a correlated acoustic signal. The results for blood pressure and HR reductions were compared during a 12-month follow-up period. The results for systolic blood pressure, diastolic blood pressure and HR indicate the efficacy of BFB for selected patients and suggest the possibility of using BFB treatment in the first stages of suspected neurogenic hypertension.
The authors show the case of a young drug addict patient with chronic hepatitis affected by pheochromocytoma, owing to his conditions, which was prepared preoperatively with a short term phenoxybenzamine i.v. We had no complications in the perioperative period. Our opinion is that it is possible, when necessary, to administer a short term therapy but this preparation isn't be considered a standard therapeutic program.