Aspirin enhances the antihypertensive effect of captopril in spontaneously hypertensive rats.
Activation of renal or vascular prostaglandin mechanisms (or both) has been proposed to contribute to the antihypertensive action of captopril. In conscious spontaneously hypertensive rats (SHR) studied in the established phase of hypertension, the blood pressure-lowering effect of captopril, 30 mg/kg/12 hr p.o. given for 7 days, was greatly enhanced by the addition of aspirin, 200 mg/kg/day s.c. Systolic blood pressure decreased from 185 +/- 6 and 182 +/- 4 to 135 +/- 3 mm Hg in rats treated, respectively, with captopril and aspirin or captopril alone, and was unaltered by either vehicle or aspirin alone. Water intake was inconsistently affected by captopril but was increased (p less than 0.01) by aspirin and was even higher after captopril-aspirin treatment (p less than 0.01). Urine volume was elevated in all 3 drug-treated groups, increasing threefold after captopril-aspirin treatment. Excretion of sodium and potassium was unchanged by any treatment regimen. In the vehicle group, prostaglandin F2 alpha excretion, measured by radioimmunoassay, ranged between 65 and 93 ng/8 hr and was twofold to fourfold higher than that of prostaglandin E2. Prostaglandin F2 alpha was unaffected during captopril treatment, whereas prostaglandin E2 excretion decreased to 12 +/- 2 ng/8 hr (p less than 0.01) by Day 7. Long-term aspirin treatment, either with or without captopril, did not cause sustained inhibition of renal prostaglandin excretion, although a transient effect occurred within the first four hours of administration. These results indicate 1) aspirin potentiates the blood pressure-lowering effect of captopril in SHR, an effect that is associated with a threefold increase in urine flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Quilley
C P
CP
Chiba
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Quilley
J
J
McGiff
J C
JC
D000818:Animals; D001241:Aspirin / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use*; D004231:Diuresis / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D004357:Drug Synergism; D004573:Electrolytes / Q000652:urine; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D008297:Male; D011453:Prostaglandins / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood
D004573:Electrolytes; D011453:Prostaglandins; D002216:Captopril; D012083:Renin; D001241:Aspirin