Interrelations of the renal kallikrein-kinin system and renal prostaglandins in the conscious rat. Influence of mineralocorticoids.
To investigate possible relationships between mineralocorticoids, the renal kallikreinkinin system, and renal prostaglandins, we studied the effects of aldosterone and deoxycorticosterone acetate (DOCA) and of an inhibitor of kallikrein, aprotinin, on the urinary excretion of kallikrein and prostaglandin E-like substance (PGE) by the conscious rat. Aldosterone (0.25 mg/day, sc), injected into six rats for 14 consecutive days, increased PGE and kallikrein excretion from 52.3 +/- 8.7 (mean +/- SE) ng/day and 29.8 +/- 3.0 U/day to 141.5 +/- 30.7 ng/day (P less than 0.02) and 105.6 +/- 28.1 U/day (P less than 0.05), respectively. Similarly, injections of DOCA (5 mg/day) into 14 rats increased the excretion of PGE and kallikrein, measured before and after 10 days of treatment, from 41.6 +/- 3.9 ng/day and 39.4 +/-4.9 U/day to 194.3 +/- 20.7 ng/day (P less than 0.001) and 90.6 +/- 14.7 U/day (P less than 0.001), respectively. Injections of aprotinin for 4 days (50,000 KIU twice daily, sc) in conjunction with DOCA into eight rats pretreated with the steroid for 10 days decreased the urinary excretion of kallikrein and PGE, measured on the 4th day of aprotinin administration, by 61% (P less than 0.01) and 80% (P less than 0.001), respectively. Urinary potassium excretion decreased throughout the course of aprotinin treatment, whereas sodium excretion and urine volume decreased during the first 2 days but subsequently returned toward control values. This study demonstrates that mineralocorticoids enhance the urinary excretion of PGE, and this effect appears to be a consequence of activation of the renal kallikrein-kinin system by the steroids. Thus, changes in the intrarenal activity of the kallikrein-kinin system may modulate renal prostaglandin release.
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology*; D007610:Kallikreins / Q000652:urine*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D014677:Pharmaceutical Vehicles / Q000494:pharmacology; D011188:Potassium / Q000097:blood / Q000652:urine; D011453:Prostaglandins / Q000378:metabolism*; D011458:Prostaglandins E / Q000652:urine*; D051381:Rats; D012715:Sesame Oil / Q000494:pharmacology; D012964:Sodium / Q000097:blood
D014677:Pharmaceutical Vehicles; D011453:Prostaglandins; D011458:Prostaglandins E; D003900:Desoxycorticosterone; D000450:Aldosterone; D012715:Sesame Oil; D007611:Aprotinin; D012964:Sodium; D007610:Kallikreins; D011188:Potassium