Short- and long-term efficacy of a calcium-antagonistic agent (nifedipine) combined with methyldopa in the treatment of severe hypertension.

Nifedipine induces a potent vasodilating and antihypertensive effect in man through a calcium- antagonistic action.The drug was tested alone and in combination with methyidopa in 23 subjects with uncomplicated primary severe hypertension (diastolic pressure > 120 mm Hg) in a short-and long-term therapeutic trial.Hourly pressure readings during the short-term period showed that the antihypertensive response to nifedipine (10 mg orally) is maximal within 40 minutes and lasts for 8-12 hours.When nifedipine is administered every 6 hours the tendency of blood pressure to rise after each dose is repressed by the next dose, so that pressure remains significantly reduced throughout the 24 hours; when methyidopa is combined (250 mg four times daily) blood pressure is further reduced toward normal, without significant fluctuations during the day.After 10 days of drug combination, the antihypertensive response was mediated through reduction of peripheral vascular resistance associated with increase in cardiac output.Renal function was unchanged or improved and sodium retention and plasma volume expansion were not promoted.In six patients with very severe hypertension (diastolic pressure > 140 mm Hg) complicated by cardiac failure, a dosing regimen every 4 hours of the two compounds promptly relieved dyspnea and lung congestion and, within 2-3 days, stabilized blood pressure to an average of 150/98 mm Hg.Persistence of the antihypertensive efficacy of this drug combination in a dosing regimen every 6 hours and its beneficial effects on heart size, ECG and fundi were documented in 22 subjects (four of whom belonged to the decompensated group) who completed a 12-month follow-up.A tenden- cy in seven cases to ankle pitting or edema was the major side effect of nifedipine; the cause of this effect remains obscure.