Urinary kallikrein activity and renal vascular resistance in the antihypertensive response to thiazide diuretics.
To evaluate the mechanism of chronic thiazide diuretic action in hypertension, we treated 19 essential hypertensive white men for 1-month periods on placebo alone and hydrochlorothiazide alone. During therapy, mean arterial pressure (MAP) fell, but radioisotopically determined intravascular volume remained unchanged, suggesting other mechanisms of thiazide action upon blood pressure. In the renal circulation, thiazides did not change renal plasma flow or glomerular filtration rate, but renovascular resistance was diminished, probably at the afferent arteriole. Concomitant with the decline in blood pressure and renovascular resistance, urinary kallikrein excretion increased, from subnormal (hypertensive) levels back into the normal range. The kallikrein increase did not correlate with changes in plasma aldosterone. In addition, patients with blood pressure responses (reduction greater than or equal to 10%) to thiazides (n = 12) had greater increases in kallikrein excretion than those without such a blood pressure decrement (n = 7), suggesting a role for renal kallikrein in the hypotensive response to thiazide diuretics.
D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D004573:Electrolytes / Q000378:metabolism; D006439:Hemodynamics; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology* / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy*; D007610:Kallikreins / Q000502:physiology / Q000652:urine*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011187:Posture; D014655:Vascular Resistance / Q000187:drug effects
D004573:Electrolytes; D010919:Placebos; D006852:Hydrochlorothiazide; D000450:Aldosterone; D007610:Kallikreins