Antihypertensive and renal effects of captopril in spontaneously hypertensive rats: evidence against a role of the kallikrein-kinin system.
Inhibition of the kallikrein-kinin system with aprotinin, and measurements of urinary kallikrein and kinin excretion, were used to examine a possible involvement of endogenous kinins in mediating the acute antihypertensive and renal actions of captopril in conscious, unstressed spontaneously hypertensive rats (SHR). Captopril, 30 mg/kg + 300 micrograms/kg/min, caused an acute significant decrease in mean arterial pressure. Urinary kallikrein excretion tended to decrease, while kinin excretion tended to decrease, while kinin excretion tended to increase after captopril, without reaching statistical significance. Renal water and electrolyte excretion remained practically unchanged. Aprotinin, 1,000 KIU/kg/min, had no effect on mean arterial pressure, whereas it decreased urinary kallikrein activity to undetectable levels and lowered kinin excretion by 21% (p less than 0.05). Urine flow remained unchanged, but sodium/potassium excretion ratio increased significantly during aprotinin infusion. When captopril and aprotinin were infused in combination, the decrease in mean arterial pressure was not significantly different from that seen when captopril was given alone. Although urinary kallikrein activity decreased below the detection limit of our assay, urinary kinin, as well as water and electrolyte excretion, remained relatively stable during the combined infusion. The present results provide direct evidence that the acute antihypertensive effect of captopril in conscious SHR is probably not due to an increased kinin accumulation secondary to the inhibition of kininase II. Our findings also suggest that under basal conditions intrarenal renin-angiotensin and kallikrein-kinin systems may play a minor role, if any, in the regulation of renal water and electrolyte excretion.
D000818:Animals; D000959:Antihypertensive Agents; D007611:Aprotinin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007610:Kallikreins / Q000502:physiology*; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D007705:Kinins / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood
D000959:Antihypertensive Agents; D007705:Kinins; D007611:Aprotinin; D002216:Captopril; D007610:Kallikreins; D012083:Renin