Plasma noradrenaline and plasma renin activity were measured as indices of sympathetic activity and renin angiotensin system in similar groups of hypertensive patients receiving either propranolol, bendrofluazide or methyldopa. Plasma renin activity was similar in the propranolol and methyldopa groups and significantly lower (p less than 0.01) in both these groups than the diuretic treated subjects. Plasma noradrenaline was significantly lower (p less than 0.01) on methyldopa than either propranolol or bendrofluazide. These different effects on the renin angiotensin system and the sympathetic nervous system of these drugs may be relevant in the choice of long term therapy in hypertension.

The effect of pretreatment with the tricyclic antidepressant desmethylimipramine (DMI) 75 mg daily for 3 days on the action of oral methyldopa 750 mg was investigated in a double blind crossover design in volunteers. DMI pretreatment caused a small but not significant increase in supine systolic and diastolic blood pressure and heart rate. However, the effects of methyldopa on lying and standing blood pressure and heart rate were not markedly altered by pretreatment. In particular, the fall in standing blood pressure after methyldopa was present with and without DMI and the sedative action of methyldopa was similar. DMI alone reduced saliva production. No evidence was found that tricyclic antidepressant drugs significantly modify the hypotensive effect of methyldopa in man.

1 Methyldopa has a short plasma half‐life, but longer duration of antihypertensive effect. A single bedtime dose of methyldopa has been recommended to improve compliance and decrease side effects. 2 This double‐blind crossover study was designed to determine the duration of antihypertensive effect of methyldopa by comparing hourly supine and standing blood pressures, throughout the day during placebo, single morning dose, and single evening dose methyldopa therapy in 10 patients. The major side effects, drowsiness and dry mouth were assessed by visual analogue scale. Exercise blood pressures were measured 6, 12, 18 and 24 h after the dose. 3 The antihypertensive effect of methyldopa peaked after 6‐9 h and declined thereafter with a half‐life of approximately 10 h. Little antihypertensive effect remained 24‐26 h after the dose. The time course of the reduction in blood pressure during exercise and of the major side effects paralleled the antihypertensive effects. 4 The results suggest that the duration of antihypertensive effect of methyldopa is long enough to permit twice daily dosing, but that single daily dosing cannot be recommended for most patients. The study illustrates the importance of knowing the time of the last methyldopa dose when assessing blood pressure measurements in patients taking the drug.

The effects of intravenous strophanthin K (0.125 and 0.25 MG) and lanatoside C (0.4, 0.8 and 1.6 mg) on systolic time intervals (STI) and impedance plethysmographic (IP)P values were studied in ten patients with compensated coronary heart disease. The heart rate decreased significantly during a two-hour study in the lying position after both glycosides and placebo; the systemic blood pressure remained unchanged. Electromechanical systole (QS2), left ventricular ejection time (LVET) and preejection period (PEP), corrected for heart rate (QS2I, LVETI, PEPI), showed no change after placebo. The glycosides caused no change in LVETI. QS2I was significantly shortened only after lanatoside C 1.6 mg. PEPI and ICT were significantly shortened by both doses of strophanthin K and lanatoside C; the effects were dose-related. Taking into consideration the effects of cardiac glycosides on STI, use of the index ICT/QS1, the quotient of isovolumic contraction time and electro-mechanical delay, is proposed, because it showed quite sensitively the increase in myocardial contractility after digitalis. The effect of strophanthin K could be detected 10 minutes, and that of lanatoside C 30-40 minutes, after injection. The amplitude of the IP curve and the relative pulse volume showed positive and negative changes without any trend after administration of placebo or glycoside. The data suggests that the usual therapeutic doses of these cardiac glycosides do not cause significant changes in the peripheral circulation in patients with compensated coronary heart disease, but their action on STI is quite marked, showing a positive inotropic effect.

No abstract