Thiazide induced hypotension: the role of plasma volume reduction and the urinary kallikrein system.

The hypotensive response the thiazide diuretics was studied in 15 males with moderate essential hypertension and correlated with serial changes in plasma volume, weight, plasma renin activity, urinary aldosterone, and urinary kallikrein, both total and activity. A greater than 10 mmHg fall in mean arterial pressure after four weeks of treatment defined the responders to therapy (n = 10) while all others were considered non-responders (n = 5). In responders, the fall in mean arterial pressure was accompanied by sustained reduction in plasma volume and weight. No sustained fall in plasma volume was noted in non-responders. Plasma renin activity and urinary aldosterone excretion increased in responders but not in non-responders. Urinary kallikrein, both total and active, increased in the responders but remained unchanged in the non-responders. The results are consistent with the hypothesis that a sustained reduction in plasma volume is necessary for the maintenance of a hypotensive response to thiazides. Stimulation of the renal kallikrein-kinin system may be necessary to balance the antinatriuretic and pressor effects of the renin-angiotensin-aldosterone system. If unopposed, this system would return plasma volume and blood pressure to pretreatment levels.