Stefano Soro

Effects of alpha-adrenergic and beta-adrenergic receptor blockade on lipid metabolism

The role of lipoprotein lipase in the pathophysiology of lipid changes during alpha-receptor or beta-receptor blockade was evaluated in this clinical trial. Thirty hypertensive patients were given 2 mg of prazosin twice daily or 100 mg of metoprolol twice daily for 10 weeks, according to an open, randomized protocol. Both drugs were effective in reducing arterial blood pressure (from 153 +/- 16/102 +/- 6 mm Hg to 146 +/- 12/92 +/- 8 mm Hg with prazosin and from 158 +/- 17/103 +/- 8 to 144 +/- 14/94 +/- 10 mm Hg with metoprolol). Prazosin significantly reduced total plasma cholesterol from 202 +/- 39 to 188 +/- 36 mg/dl and increased high-density lipoprotein cholesterol from 36 +/- 8 to 40.5 +/- 11 mg/dl. Prazosin did not affect plasma triglycerides levels, whereas patients taking metoprolol had a slight rise in these levels, from 122 +/- 42 to 142 +/- 57 mg/dl, along with a decrease in high-density lipoprotein cholesterol from 37 +/- 10 to 31 +/- 8 mg/dl. The concentration of apoprotein B did not change significantly with either treatment. Lipoprotein lipase activity increased in the prazosin group from 28.4 +/- 16 to 37.7 +/- 14 mumol/liter per minute (p less than 0.01), but did not change significantly (29.9 +/- 12 versus 32.8 +/- 8 mumol/liter per minute) in patients treated with the beta blocker. These data, which confirm previous reports of serum lipid changes during antihypertensive therapy, suggest that alpha1 blockers may interfere with lipoprotein lipase, possibly by reducing its catecholamine-mediated inactivation.

Antihypertensive and cardiovascular effects of nitrendipine: a controlled study vs. placebo.

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.

Age related antihypertensive effect of nitrendipine, a new calcium entry blocking agent

SummaryThe effect of nitrendipine 20 mg o.d., a new calcium entry blocker similar in structure to nifedipine, on blood pressure has been evaluated in 14 patients (aged 24–62 years) with uncomplicated mild or moderate arterial hypertension. A significant decrease both in systolic (160±12 at baseline vs 141±8 mm Hg, p<0.001) and diastolic (106±8 vs 93±3 mm Hg, p<0.001) blood pressure was observed at the end of 8 weeks of nitrendipine treatment. An inverse correlation was found between age and the reduction in diastolic blood pressure (r=0.772, p<0.001 as absolute reduction; r=0.791, p<0.001 as percentage reduction versus baseline). This peculiar characteristic differentiates the effect of nitrendipine from that of other calcium entry blockers, which appear to be more effective in older patients.

Cardiovascular Effects of Ketanserin, A New Antiserotonergic Agent in the Treatment of Arterial Hypertension

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.

The effects of nicardipine on sodium and calcium metabolism in hypertensive patients: a chronic study.

There is evidence in the literature that calcium entry blockers are able to affect calcium‐dependent hormone secretion and therefore can influence sodium and calcium metabolism.

Adrenergic blocking agents and lipoprotein lipase activity

Lipoprotein lipase activity, total serum cholesterol and triglycerides, HDL cholesterol were determined before and after two weeks of treatment with a low dose of an α1-blocking agent (prazosin) or of a β-adrenergic-blocking drug (metoprolol). Lipoprotein lipase activity was almost doubled after prazosin (p < 0.02) and practically unchanged after metoprolol, at a time and at a drug dosage when only minor changes in blood pressure and serum lipids were detectable. HDL cholesterol was slightly but significantly increased after prazosin (p < 0.05). Heart rate was increased after prazosin (p<0.05) and decreased after metoprolol (p<0.01).

Resting blood pressure and cardiovascular response to sympathetic stimulation in adolescents

The prevalence of significant hypertension in childhood may be higher than expected. We have measured sitting blood pressure in 168 11-yr-old children attending a pre-high school in the Neapolitan area on four occasions over a 3-month period. We have also measured blood pressure and heart rate during a mental arithmetic test and during isometric exercise. Prevalence of significant hypertension (diastolic blood pressure 82-90 mmHg) was 13% at the first visit and decreased to 6.5% at the last visit; prevalence of severe hypertension (diastolic blood pressure greater than or equal to 90 mmHg) decreased from 5.4% to 1.2% from the 1st to the 4th visit. No sex-related difference was observed. A more frequently positive family history of hypertension (50% vs 30% in the fifth and first quintile of blood pressure, respectively) and higher body weight (body mass index = 21.4 vs 19.3 kg/m2) were found in children in the 5th quintile of blood pressure distribution. Blood pressure increased during mental arithmetic by 10/13% of the resting values in the first quintile and by 6/11% in the last one during mental test; during handgrip the increase was of 20/37% and 24/46%, respectively: differences between quintiles did not reach statistical significance. These data show that about 8% of a Neapolitan sample of school population have high blood pressure levels, while no difference in vascular reactivity to sympathetic stimulation was detected in children with higher blood pressure.

Effect of lacidipine, a long-acting calcium antagonist, on hypertension and lipids: a 1 year follow-up.

SummaryThe effect of lacidipine, a dihydropyridine calcium antagonist on lipid metabolism, has been followed in 8 patients with uncomplicated mild to moderate essential hypertension treated for up to 14 months.There were significant reductions in the systolic and diastolic pressures, from 167/102 to 146/91 mmHg at 2 months, and to 137/85 mmHg at the end of the study. Blood lipid concentrations did not change during the observation period (cholesterol 5.1 vs 5.3 mmol·l−1, triglycerides 1.1 vs 1.0 mmol·l−1, HDL-cholesterol 1.1 vs 1.2 mmol·l−1).The results show that lacidipine did not affect lipid metabolism and suggest that calcium antagonists may be safely prescribed for a prolonged period to patients with combined hypertension and hyperlipidaemia.

Study with the competitive 5-HT2-serotonergic antagonist ketanserin.

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.

Antihypertensive efficacy of the combination of ketanserin + thiazide in hypertensives older than 50 years.

The antihypertensive effect of the combination of ketanserin, a new antiserotonergic agent, and thiazide has been evaluated in 35 patients with arterial hypertension of mild to moderate degree in the >50-year-old age group. Twenty patients were given ketanserin (20 mg) + hydrochlorothiazide (25 mg) (treatment A) while the others were given ketanserin (40 mg) + hydrochlorothiazide (12.5 mg) (treatment B) once daily, for a period of 6 weeks. Twenty-four-hour blood pressure, measured by an automatic recorder, was significantly reduced by both combinations. In particular, treatment A reduced blood pressure from 169 ± 15/95 ± 6 mm Hg before treatment to 146 ± 11/83 ± 8, 149 ± 13/82 ± 10, 143 ± 12/81 ± 9, and 151 ± 14/84 ± 7 mm Hg at 2, 6, 8, and 24 h, respectively, after the last dose of drug. With treatment B, blood pressure was reduced from 167 ± 11/97 ± 7 mm Hg before treatment to 152 ± 12/89 ± 8, 151 ± 15/85 ± 8, 150 ± 16/86 ± 8, and 158 ± 13/91 ± 7 mm Hg at 2, 6, 8, and 24 h, respectively. Heart rate was not affected by both treatments despite the fact that ketanserin has been proved to induce a marked vasodilation. Cardiac workload (systolic blood pressure × heart rate) was slightly reduced by the treatments. Treatment A only induced transient dizziness after the first dose of drug; treatment B, on the other hand, induced drowsiness and more marked dizziness, which in one case was also observed after repeated doses of the drug. These data, therefore, support the hypothesis that the combination of ketanserin + thiazide, particularly at the dose of 20 + 25 mg, respectively, is an effective and well-tolerated antihypertensive treatment in patients in the >50-year-old age group.