Comparison of ketanserin and metoprolol in the treatment of essential hypertension.

Ketanserin, a serotonin receptor antagonist (S2), lowered blood pressure in patients with essential hypertension; at three months 72% (13/18) had a successful reduction in pressure. No marked orthostatic changes were noted. Older patients responded better when standing. Compared with metoprolol, ketanserin provided no significant difference in response at three months. With ketanserin, the heart rate was reduced only in the supine position, whereas it was reduced in the supine and standing positions with metoprolol. Response to ketanserin could not be predicted from baseline renin, aldosterone, or cortisol levels in blood, nor were there any changes in these factors or in plasma hydroxyindole levels with therapy. Ketanserin was generally well tolerated. Cholesterol values were significantly reduced with ketanserin, and there were no adverse hematologic or biochemical changes. Ketanserin should have a significant role in managing hypertension.

Verapamil and 24-hour ambulatory blood pressure monitoring in essential hypertension.

The antihypertensive effects of oral regular and slow-release verapamil, a calcium-channel blocking agent, were evaluated in 22 patients with mild to moderate hypertension (sitting diastolic blood pressure [DBP] 95 to 112 mm Hg). The dose required to control blood pressure varied from 80 to 120 mg, 3 times a day. All patients received regular verapamil for a further 3 to 4 months, when systolic blood pressure (SBP) and DBP had risen from the end of the open-label phase. During a double-blind phase patients were randomly assigned to continue the same dose of regular verapamil, 3 times a day, or an equivalent daily dose of sustained-release verapamil (240 to 360 mg once a day). Seven of the 11 patients on regular and 3 of the 11 on sustained-release verapamil were also taking diuretics. This antihypertensive program was continued for at least 4 weeks. During the efficacy period, 24-hour ambulatory blood pressure monitoring was carried out. Mean 24-hour SBP and DBP were 133 +/- 20 and 89 +/- 13 mm Hg, respectively, on regular and 131 +/- 22 and 87 +/- 12 mm Hg, respectively, on sustained-release verapamil. There were no statistically significant differences noted between the 2 groups. Mean SBP and DBP varied similarly during awake and sleep hours with both formulations of verapamil. With regular verapamil, SBP was 139 +/- 18 and 124 +/- 20 mm Hg and DBP 92 +/- 11 and 84 +/- 13 mm Hg during awake and sleep hours, respectively; with sustained release, SBP was 138 +/- 21 and 122 +/- 22 mm Hg and DBP 92 +/- 10 and 80 +/- 10 mm Hg during awake and sleep hours, respectively. Heart rate fell during the entry period and continued during the entire study period. No other adverse effects were noted during the double-blind phase. In summary, verapamil is an effective antihypertensive medication and can be administered once a day as a sustained-release preparation; it is most useful in patients in whom adrenergic blocking drugs are indicated.

Antihypertensive efficacy of pinacidil--automatic ambulatory blood pressure monitoring.

Forty-three patients with mild essential hypertension were randomized into two double-blind studies: pinacidil vs. placebo or pinacidil vs. hydralazine. Pinacidil (62 +/- 18 mg/day) decreased office systolic and diastolic blood pressures from 145 to 137 mm Hg and from 98 to 89 mm Hg, respectively, after 6 weeks of therapy. Similarly, hydralazine (128 +/- 28 mg/day) reduced supine systolic blood pressure from 140 to 134 mm Hg and supine diastolic blood pressure from 93 mm Hg to 84 mm Hg. Significant tachycardia was not noted with either drug. Ambulatory blood pressure was monitored for 24 h during the placebo-washout and efficacy phases with both pinacidil and hydralazine. Mean 24-h blood pressure was 128 systolic and 81 diastolic with pinacidil and 121 systolic and 76 diastolic with hydralazine. Reduction in awake hypertensive diastolic blood pressure was significant for both pinacidil and hydralazine. Normal sleep diastolic blood pressure was not reduced by pinacidil but was reduced by hydralazine. Side-effects with both drugs included edema, headache, and palpitations. These data demonstrate that pinacidil is as effective an antihypertensive agent as hydralazine.

Evaluation of pindolol dosage in hypertension by automatic indirect BP monitoring.

Pindolol, a nonselective beta-adrenergic blocking drug, lowered systolic and diastolic BP equally well during once-daily and twice-daily dosage. Side effects were few. Absence of supine bradycardia distinguished this drug from other beta-adrenergic blockers and likely was attributable to the agent's intrinsic sympathomimetic activity. Blood pressure variability was less during therapy. Automatic indirect BP monitoring reliably confirmed office and home BP recordings and indicated good control throughout waking and sleeping periods.

Pindolol--a new beta-adrenergic blocking agent with intrinsic sympathomimetic activity in the management of mild and moderate hypertension.

Pindolol, a well-tolerated noncardioselective beta-adrenergic blocking drug, effectively reduced blood pressure in patients with mild to moderate hypertension without causing orthostatic hypotension. In common with other beta-adrenergic blocking agents, pindolol blocked the normal increase in the standing pulse rate. The drug, however, did not decrease the supine pulse rate, a feature that can be interpreted as evidence of the postulated intrinsic sympathomimetic activity of pindolol.

Prospective study of immune response to hydralazine and development of antideoxyribonucleoprotein in patients receiving hydralazine.

To examine the relationship between the immune responses to hydralazine, a drug known to induce systemic lupus erythematosus, and to deoxyribonucleoprotein (DNP) we followed prospectively 21 hypertensive patients treated with hydralazine for the first time. Within one year, antibodies to hydralazine developed in 16 of these patients and anti-DNP in seven of these. In one patient whose serum had a positive antinuclear antibody test prior to treatment, a mild hydralazine systemic lupus erythematosus syndrome developed preceded by rises in the levels of both anti-hydralazine and anti-DNP. Studies by radioimmunoassay on serums of three additional patients, not followed in this study but known to have hydralazine-induced systemic lupus erythematosus, revealed no evidence for either (1) cross-reactivity between anti-DNP and anti-hydralazine or (2) antibodies specific for a hydralazine-DNP complex. In some way, perhaps related to the mechanism by which carrier molecules enhance the immunogenuity of haptens, hydralazine increases the antigenicity of DNP. This effect depends on the development of immunity to hydralazine as well.

One-year graduated exercise program for men with angina pectoris. Evaluation by physiologic studies and coronary arteriography.

Eight men, 45 to 50 years of age, with mild stable angina pectoris, participated in a graduated exercise program. Coronary arteriography, left ventriculography, left ventricular hemodynamics at rest and during supine leg exercise, treadmill testing with electrocardiographic monitoring, and measurement of oxygen uptake were obtained before and 1 year after the exercise training program. No change was noted in the arteriographic appearance of coronary artery lesions or of collateral circulation. Left ventricular performance, assessed by qualitative left ventriculography and the hemodynamic response of the left ventricle to supine leg exercise, was unchanged after the training program. Oxygen consumption for a given repetitive work load during treadmill exercise decreased. Two patients with a pretraining exercise ECG positive for ischemia reverted to a normal response after the exercise program. All had a decrease in angina, an increase in self-esteem, and a more positive attitude toward their work and their disability.