In 10 patients with primary arterial hypertension of mild or moderate degree, ketanserin, a competitive antagonist of serotonin receptors. was given for a period of 4 weeks, 40 mg twice daily. In a control group, patients were given 100 mg twice daily of metoprolol for 4 weeks for each treatment. A randomized double-blind crossover model was used. Blood pressure and heart rate were measured at rest and during exercise testing on a bicycle; peripheral blood flow was measured by strain-gauge plethysmography. A slight reduction in resting systolic and diastolic blood pressure without change in heart rate was observed during treatment with ketanserin. Cardiac workload during exercise test did not change over the observation period. A slight increase in resting blood flow to the lower limbs, with a decrease in peripheral resistance was demonstrated by strain-gauge plethysmography.
Changes in hemodynamic variables regulating systolic function were assessed by M-mode echocardiography, under 2D control, in 11 patients with primary uncomplicated hypertension treated with nicardipine (60 mg/daily). At the end of treatment (8 weeks) blood pressure and end-systolic stress were greatly reduced (p less than 0.001), and systolic fractional shortening was increase (p less than 0.02). The percentage increase in fractional shortening was correlated with a decreased in end-systolic stress (r = 0.67). The index of left ventricular performance (systolic pressure/end-systolic dimension ratio) was reduced: no variation was found in the hypertrophy-independent index of the inotropic state (systolic pressure/end-systolic dimension ratio normalized for posterior wall thickness). No change in the inotropic state was caused by a negligible sympathetic reflex outflow: heart rate also remained unchanged. The only index of left ventricular hypertrophy which was slightly reduced after two months of treatment was left ventricular mass (p less than 0.001). In conclusion, the short-term treatment with nicardipine, in hypertensive patients, showed powerful effects in the improvement of systolic function; the possible regression of left ventricular hypertrophy must be confirmed in long-term therapy.
The antihypertensive and cardiovascular effects of nitrendipine, a calcium entry blocker similar to nifedipine, have been evaluated in a double-blind, placebo-controlled study in 20 patients with hypertension. At baseline and at the end of the 8-week period (nitrendipine, 20 mg once a day, or placebo, 1 tablet once a day) the following parameters were measured: systolic and diastolic blood pressure (BP) and heart rate (HR) at rest by an automatic recorder; BP, HR, and cardiac workload (systolic BP × HR) during exercise testing on a bicycle; left ventricular mass (LVMe according to the method of Devereux) and cross-sectional area (CSA), and main parameters of systolic function (end diastolic volume, end systolic volume [ESV], and ejection fraction [EF]) by M mode echocardiography. There was a significant decrease in BP at rest (163/108 vs. 144/92 mm Hg; P < 0.001) and during exercise in subjects receiving nitrendipine, while placebo did not modify these parameters. LVMe (from 195 to 188 gm; P < 0.01) and CSA (from 20.2 to 19.8 cm2; P < 0.05) were reduced by nitrendipine, which also improved cardiac performance (ESV fell from 44 to 38 ml [P < 0.001] and EF fell from 62% to 66% [P < 0.01]). No effect was observed in the placebo group. Our results indicate that nitrendipine is a powerful antihypertensive agent that also improves cardiac performance and slightly but significantly reduces left ventricular mass. Clinical Pharmacology and Therapeutics (1985) 38, 434–438; doi:10.1038/clpt.1985.200
Ketanserin, an investigational, antiserotonergic agent, at a dose of 40 mg bid was given to 18 patients with mild to moderate primary hypertension in a randomized, double‐blind, crossover study, with 100‐mg metoprolol bid for four weeks each. The following parameters were evaluated: blood pressure, heart rate, cardiac workload (product of systolic blood pressure and heart rate during bicycle exercise), systolic time intervals, and peripheral blood flow (by strain‐gauge plethysmography). Significant reductions in diastolic and concomitant slight decreases in systolic blood pressure without changes in heart rate were observed during ketanserin treatment; cardiac oxygen demands during exercise test did not change, however. Pre‐ejection period and left ventricular ejection time were unchanged, while significant increase in rest flow to the lower limbs and decrease in peripheral resistance were demonstrated by strain‐gauge plethysmography. The results indicate that ketanserin has vasodilating properties and hypotensive activity that may be useful in the management of patients with essential hypertension.
Indapamide, a sulphonamide derivative, was prescribed for 8 weeks at low dose (2.5 mg once a day) to 14 hypertensive patients in order to investigate its effects on systolic and diastolic blood pressure (SBP, DBP), cardiac function and peripheral arterial resistance (PAR). During treatment we observed decreases in both SBP and DBP without any change in HR in the supine and standing positions and on exercise. As a result cardiac work was significantly reduced. Slight changes in pre-ejection period (PEP) and left ventricular ejection time (LVET) along with a more significant decrease in rate of rise of left ventricular pressure (DBP to PEP ratio) were observed during treatment. An increase in RBF and a decrease in PAR were also detected in the peripheral circulation. These findings may indicate that indapamide antagonizes the cardiovascular effects of catecholamines.
