Hemodynamic and neurohumoral factors in the response of hypertensives to hydrochlorothiazide therapy.

We investigated the roles of the renin-angiotensin-aldosterone axis, the sympathetic nervous system, and the responses of the forearm vascular bed in the antihypertensive action of hydrochlorothiazide. Plasma renin activity, aldosterone, catecholamines, blood pressure, and forearm blood flow were measured before and after 8 weeks of hydrochlorothiazide therapy in 21 hypertensive patients whose blood pressures responded to the diuretic, and were then compared to a similar group of 19 hypertensives who did not respond to the thiazide therapy. Dietary salt intake was stable and comparable for the two groups. In the responsive patients, administration of the diuretic caused a significant fall in supine systolic and diastolic blood pressure and forearm vascular resistance, with constant forearm blood flow. No significant changes were noted in these parameters in the non-responsive group. Plasma renin activity and aldosterone concentration was increased in both groups to a comparable extent but plasma norepinephrine and epinephrine concentrations were increased to a greater extent (p less than 0.01) in the responsive group. Heart rate did not change significantly in either group in spite of significant increases in circulating epinephrine. The results are consistent with minimal thiazide-induced volume and salt depletion in either study group. The reduction in blood pressure and forearm vascular resistance observed in the responsive group appears to be the result of diminished target-organ sensitivity towards catecholamines and possibly angiotensin II.