Myocardial meta-[125l]iodobenzylguanidine uptake in awake genetically hypertensive rats at different ages: an autoradiographic study.

The purpose of this work was to evaluate changes in myocardial meta-[125I]iodobenzylguanidine ([125I]MIBG) uptake and distribution with age in awake spontaneously hypertensive rats (SHR) with respect to Wistar-Kyoto (WKY) rats. Rats were randomly divided into two groups, one for measuring myocardial [125I]MIBG uptake and distribution 4 h after its injection and the second for evaluating myocardial catecholamine concentrations. Mean arterial blood pressure, cardiac hypertrophy index (heart/body weight ratio), and heart rate were significantly higher with increasing age in SHR compared with matched WKY rats. Myocardial catecholamine concentrations and turnover did not differ between the two strains and were significantly decreased with increasing age. Myocardial [125I]MIBG uptake determined by gamma counting was similar in WKY rats and SHR and did not vary significantly with age when expressed as uptake density. However, in both strains of rats, [125I]MIBG uptake determined by autoradiography was significantly greater at the base of the heart than at the apex and midventricular levels, and the uptake values of young rats were significantly higher than those of older rats. In 21-week-old WKY rats and SHR, the highest [125I]MIBG uptake values were found in the right ventricle. Thus, quantitative autoradiography allowed detection of significant changes in myocardial [125I]MIBG uptake and showed its heterogeneous distribution in the rat heart.

[Comparative effects of captopril and atenolol on lipid metabolism in hypertensive hypercholesterolemic patients treated with pravastatin. A multicenter controlled trial]. / Effets comparés du captopril et de l'aténolol sur le métabolisme lipidique chez des patients hypertendus hypercholestérolémiques traités par pravastatine. Essai multicentrique contrôlé.

OBJECTIVES: A randomized double-blind trial was conducted in hypertensive subjects with hypercholesterolemia treated with pravastatin in order to compare the effects of captopril and atenolol on lipid metabolism. METHODS: After a pre-inclusion period, 147 eligible subjects (64 men and 83 women, age range 32-74 years) were randomized into two groups and given, in a double-blind trial, either captopril (50 mg/d) or atenolol (50 mg/d) for 6 months. The controlled trial was followed by an open trial in 120 subjects for 6 more months. Laboratory tests for lipid metabolism were performed at inclusion and at 6 months. RESULTS: Control of blood pressure was satisfactory and similar in the two groups. Lipid tests were performed both in local and a centralized laboratory with good interlaboratory correlations. High density lipoprotein (HDL)-cholesterol remained unchanged in the captopril group declined slightly in the atenolol group. Total cholesterol increased moderately in both groups. Triglycerides increased somewhat in the captopril group and significantly more in the atenolol group. These results were maintained during the open trial. Most of the undesirable effects were benign and did not require treatment. CONCLUSION: The effects of captopril and of atenolol are not diminished in combination regimens with pravastatin. The antihypertensive efficacy was similar for the two treatments, but the effect on lipid metabolism was more favorable with captopril.

Comparison of the effects of captopril and nicardipine on insulin sensitivity and thrombotic profile in patients with hypertension and android obesity. CaptISM Study Group. Captopril Insulin Sensitivity Multicenter Study Group.

Hypertension is often related to metabolic disorders, such as android obesity, glucose intolerance, dyslipidemia, and hyperinsulinism (X syndrome). Insulin resistance (IR), described as the common link among these disorders, could contribute to an increase in coronary risk. The euglycemic insulin clamp technique has been used to show that different classes of antihypertensive agents have different effects on IR. The purpose of this multicenter study was to compare the effects of captopril to those of nicardipine on insulin profile using the oral glucose tolerance test (OGTT), a routine-feasible test. After a 1-month single-blind placebo period, 154 patients with hypertension and android obesity were randomized to 3 months of double-blind therapy with either 50 mg captopril twice daily (n = 77) or 50 mg nicardipine twice daily n = 77). An OGTT with an assay of insulin was performed before and after active treatment. Lipid parameters, Factor VII (F VII), fibrinogen, plasminogen activator inhibitor 1 (PAI-1), and insulin-like growth factor I (IGF-I) were measured at the same time. After 3 months of treatment, the changes from baseline in mean +/- SD values for the insulin area under the curve (AUC) were -24.8 +/- 107.4 microIU x h/mL (-15.2%) for captopril v 6.1 +/- 98.6 microIU x h/mL (4.8%) for nicardipine (P = .072). Changes in peak insulin values were -18.3 +/- 86.2 microIU/mL (-14%) for captopril v 6.7 +/- 79.4 microIU/mL (6.6%) for nicardipine (P = .070).(ABSTRACT TRUNCATED AT 250 WORDS)

[Left ventricular relaxation and hypertension. Effect of captopril on gamma-angiographic parameters]. / Relaxation ventriculaire gauche et hypertension artérielle effet du captopril sur les paramètres gamma-angiographiques.

In order to evaluate the action of captopril on left ventricular filling in hypertension, 14 hypertension (158 +/- 10/101 +/- 5 mmHg) patients aged 51 +/- 6 years were investigated by Technetium 99m gamma-angiography. The time/activity curve was used to determine the maximum filling rate (MFR) and maximum filling time (MFT) of the ventricle before and after treatment with captopril (mean dose : 44 +/- 26 mg/day for 7 months). Blood pressure was significantly lowered by treatment and there was a decrease in left ventricular mass from 128 +/- 17 to 118 +/- 15 g/m2 (p = 0.07). Maximum filling rate was accelerated by treatment from 2.27 +/- 0.57 to 2.57 +/- 0.43 VTD . s-1, p = 0.005). This variation was due essentially to half of the patients, suggesting an "all or nothing" type response. Maximum filling time did not vary. The basic question raised by this type of study is to know whether the improvement in the available relaxation parameter, MFR, was associated with actual improvement in filling, which is the true aim. Although the explanations offered for the observed findings are hypothetical, taking into account of all the trial data together with the morphological data provided by echocardiography suggests that captopril does have an actual and hemodynamically significant action on filling.

[Effect of the captopril-hydrochlorothiazide combination on blood lipids. Study in a population of hypertensive hyperlipidemic patients]. / Influence de l'association captopril-hydrochlorothiazide sur les lipides sanguins. Etude sur une population d'hypertendus hyperlipidémiques.

In this placebo-controlled, randomized double-blind, parallel study the effects of the fixed captopril 50 mg + hydrochlorothiazide (HCTZ) 25 mg combination on plasma lipids were assessed in 42 hypertensive, type IIa or IIb hyperlipidaemic patients on diets. Some patients received oral hypolipidaemic treatment and some did not. Blood pressure and plasma lipids levels were measured before and after 1, 2 and 3 months of treatment. From the first month onward blood pressure decreased more in the treated group than in the placebo group (P < 0.05). Neither the combination nor the placebo altered the following parameters of lipid metabolism: total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein A1 and apolipoprotein B. The combination was well tolerated; 2 patients in each group had one or several adverse events. The results of this study show that treatment with the captopril-HCTZ combination in hypertensive, hyperlipidaemic patients has no influence on the normolipidaemic effects of diet and lipid-lowering treatment.

Effects of celiprolol, a cardioselective beta-blocker, on respiratory function in asthmatic patients.

The aim of this study was to compare the pulmonary effects of a single dose of celiprolol 400 mg, versus bisoprolol 20 mg and the combination of celiprolol 400 mg plus propranolol 40 mg versus placebo plus propranolol 40 mg. We conducted a double-blind randomized cross-over study in 10 stable asthmatic patients (mean age +/- SD 31 +/- 7 yrs) with forced expiratory volume in one second (FEV1): 2.5 +/- 0.7 l. A three-day washout period preceded each treatment period. Measurements of respiratory function were done before treatment and after 90, 120 and 180 min. There was a significant increase of FEV1 (+12%) and forced vital capacity (FVC) (+8%) after celiprolol (p less than 0.05) and a decrease of FEV1 (-9%) after propranolol. Concerning the combination, celiprolol inhibits the bronchoconstrictor effects of propranolol. We conclude that celiprolol has bronchosparing properties in asthmatic patients, and even improves some of the ventilatory parameters.

Anti-ischemic effects of celiprolol in patients with exercise-induced angina pectoris.

The anti-ischemic properties of the new cardioselective beta-adrenoreceptor antagonist celiprolol were investigated in an open study of 12 men (mean age: 58 +/- 6.6 years) with exercise-induced angina pectoris. After all previous anti-anginal medication had been withdrawn for at least 5 half-lives, the patients received placebo, single doses of nitroglycerin buccal spray, sublingual nifedipine, celiprolol alone, and then in association with nitroglycerin and nifedipine. Exercise tests were performed on a bicycle ergometer, with continuous electrocardiographic monitoring. Significantly more work was completed after treatment with celiprolol than at baseline (5280 +/- 2500 versus 4005 +/- 1792 kpm; P less than 0.01). There were further improvements in work completed after the addition of nitroglycerin and nifedipine. Celiprolol reduced the mean resting heart rate from a baseline value of 77.1 beats/min to 69.2 beats/min (P less than 0.01). In contrast, nifedipine induced tachycardia (82.6 beats/min). At rest, all treatments significantly reduced systolic blood pressure, but only nifedipine significantly reduced diastolic blood pressure. At the completion of the exercise protocol, celiprolol reduced the maximal systolic and diastolic blood pressure (P less than 0.05) with further decreases after the addition of nifedipine. The double product was significantly decreased by celiprolol compared with control, nitroglycerin and nifedipine. There was a further improvement of the double product after the addition of nitroglycerin to celiprolol, but the further increase after addition of nifedipine was not significant. In conclusion, it is clear that celiprolol, both alone and in combination with nitroglycerin or nifedipine, can significantly increase the work capacity of patients with exercise-induced angina pectoris and significantly reduce myocardial oxygen consumption.