Acute blood pressure and urinary responses to single dose combinations of captopril and diuretics in conscious spontaneously hypertensive rats

The present studies involved oral administration of captopril alone or in combination with individual diuretics in conscious, freely-moving spontaneously hypertensive rats (SHR). Both blood pressure (BP) and urinary fluid and electrolyte excretion were concomitantly measured. Captopril, 10 mg kg-1, caused a decrease in BP (-18 +/- 3 mm Hg) which was not significantly different from control (-10 +/- 2 mm Hg). Diuretics alone also failed to alter BP. However the BP-lowering effect of captopril was readily potentiated by concomitant administration of a single oral dose of frusemide (10 and 30 mg kg-1) in proportion to the magnitude of urinary loss. Hydrochlorothiazide at 1 and 3 mg kg-1 oral and metolazone at 0.3 and 1 mg kg-1 oral induced fluid loss similar to frusemide at 10 mg kg-1 and all produced comparable BP reduction in combination with captopril (25-32 mm Hg). Triamterene did not increase fluid excretion and was ineffective. In SHR with bilateral ureteral ligation, the synergistic effect of frusemide was abolished while that of hydrochlorothiazide still occurred with a delayed onset. It is concluded that concomitant measurement of BP and urinary excretion in conscious, freely-moving SHR is a useful technique for studying new antihypertensive drugs. Using this preparation it was found that enhancement of the acute hypotensive response to captopril with concomitant diuretic therapy occurs within 10 min and is primarily related to the fluid and Na loss, regardless of the diuretic agent used.