Antihypertensive mechanism of diuretic treatment with chlorthalidone. Complementary roles of sympathetic axis and sodium.
Twenty-three patients with untreated mild to moderate essential hypertension had on the average an abnormally increased cardiovascular pressor responsiveness to exogenous norepinephrine (NE), while plasma and urinary NE, exchangeable body sodium and blood volume were normal. An increased pressor responsiveness to angiotensin II in these patients was associated with a tendency for low plasma renin activity (PRA). Compared to placebo conditions, treatment with chlorthalidone, 100 mg/day, for 6 weeks significantly decreased blood pressure and exchangeable sodium in these hypertensive patients but not in ten normal subjects; blood volume and heart rate were unchanged in both groups. Chlorthalidone induced a marked increase in PRA, but only a mild increase in angiotensin II pressor dose. In contrast, the diuretic caused a greater increase in NE pressor dose than in plasma NE in the hypertensive group, thus improving the disturbed relationship between plasma NE and NE responsiveness in these patients. No significant modification of plasma NE and NE responsiveness occurred in diuretic-treated normal subjects. In addition to sodium and the renin-angiotensin system, the sympathetic regulatory axis seems to be involved in the antihypertensive mechanism of chlorthalidone. Thiazide-like diuretics may decrease blood pressure in essential hypertension in part by lowering an abnormally high cardiovascular NE responsiveness without causing an equivalent increase in circulating NE.
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002752:Chlorthalidone / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects*; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism*
D000804:Angiotensin II; D012964:Sodium; D012083:Renin; D002752:Chlorthalidone; D009638:Norepinephrine