Correction of altered noradrenaline reactivity in essential hypertension by indapamide

SUMMARY Fourteen patients with untreated mild to moderate essential hypertension had on average an abnormally high cardiovascular reactivity to exogenous noradrenaline and angiotensin II, while plasma noradrenaline, renin activity, exchangeable body sodium, and blood volume were normal. Treatment with a low dose of indapamide (2-5 mg/day) for six weeks decreased blood pressure by 10 % in these hypertensive patients but not in 13 normal control subjects. Plasma or blood volume and exchangeable sodium were not changed significantly; nevertheless, the latter, and body weight, tended to be decreased slightly. Though a mild reduction in extracellular sodium in both normal and hypertensive subjects appears possible, it may not per se fully explain indapamide's blood pressure-lowering effect in essential hypertension. Indapamide induced a mild decrease in angiotensin II pressor responsiveness in normal or hypertensive subjects, but a possible depressor influence from this change was probably antagonised by a concomitant pronounced increase in plasma renin activity. In hypertensive patients, the abnormally high noradrenaline ractivity was corrected by indapamide without an accompanying increase in endogenous plasma noradrenaline levels. Indapamide-induced changes in blood pressure correlated with those in noradrenaline pressor dose. It was concluded, therefore, that indapamide may decrease blood pressure in essential hypertension at least in part by lowering an abnormally high cardiovascular noradrenaline reactivity without causing an equivalent increase in adrenergic nervous activity. The pathogenesis of essential hypertension is still incompletely understood and thus the selection of drugs for its treatment has been based largely on empirical guidelines. Recent studies have suggested that essential hypertension is associated with exaggerated cardiovascular reactivity to noradrenaline in the presence of normal or sometimes even somewhat high sympathetic and renin activity' " and a normal body sodium volume state.5 6 In consequence, an agent acting preferentially on vascular sensitivity should be of therapeutic interest