The prostaglandin and kallikrein-kinin systems in mineralocorticoid escape.
To evaluate the interactions of the renal prostaglandin and kallikrein-kinin systems during mineralocorticoid escape, we administered desoxycorticosterone acetate (DOCA; 20 mg im daily for 10 days) to five normal men and then repeated the study 2-16 weeks later with simultaneous indomethacin (200 mg/day) or ibuprofen (1600 mg/day) for prostaglandin inhibition (PI). Plasma aldosterone, PRA, and urinary prostaglandin E (PGE) were measured by immunoassay; urinary kallikrein activity was measured by esterase activity. With DOCA, subjects gained 2.0 +/- 0.1 (SE) kg and retained 485 +/- 125 milliequivalents (meg) sodium; serum potassium fell from 4.6 +/- 0.2 to 3.2 +/- 0.1 meq/liter, aldosterone fell from 3.8 to 2.2 ng/dl, and PRA fell from 0.9 to 0.1 ng/ml . h (all P less than 0.05). Kallikrein increased from 6.4 +/- 1.6 to 65.3 +/- 18.8 esterase U (P less than 0.01), but PGE (820 +/- 110 vs. 780 +/- 80 ng/day) did not change. With DOCA and PI, PGE fell by 80%. Subjects again gained 2.0 kg and retained 530 +/- 106 meq sodium; aldosterone fell to 1.1, PRA fell to 0.2, and potassium fell to 3.3 (all P less than 0.05 from basal, but P less than 0.4 from DOCA alone). Kallikrein again rose to 56.0 +/- 19.2 (P less than 0.01). However, the rate of sodium retention was enhanced slightly but significantly. These studies demonstrate that with DOCA, urinary kallikrein activity increases but PGE is unaltered. The minimal effects of prostaglandin inhibition and the lack of change in PGE excretion suggest that prostaglandins do not play an important role in mineralocorticoid escape. There is no apparent interaction of prostaglandins with the kallikrein system in this model; however, the kallikrein-kinin system may still play a direct role in the escape phenomena.
D000328:Adult; D000450:Aldosterone / Q000097:blood; D003900:Desoxycorticosterone; D006801:Humans; D007052:Ibuprofen; D007213:Indomethacin; D007610:Kallikreins / Q000652:urine*; D007705:Kinins / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D011458:Prostaglandins E / Q000652:urine*; D012964:Sodium / Q000378:metabolism*
D007705:Kinins; D011458:Prostaglandins E; D003900:Desoxycorticosterone; D000450:Aldosterone; D012964:Sodium; D007610:Kallikreins; D011188:Potassium; D007052:Ibuprofen; D007213:Indomethacin