Evidence that the beta-adrenergic system and prostaglandins stimulate renin release through different mechanisms.
In normal man, converting enzyme inhibition (CEI) acutely increases plasma active renin and decreases plasma inactive renin. This reciprocal relationship suggests that conversion of inactive to active renin may be important in the acute response to stimulation of renin secretion. To determine whether the beta-adrenergic system or prostaglandins (PGs) participate in the acute effect of CEI on renin, we administered captopril (50 mg) alone and with either propranolol (P; 80 mg) or a PG cyclooxygenase inhibitor [PI; indomethacin (50 mg) or ibuprofen (800 mg)] to normal subjects ingesting a 25 meq/day Na diet. Supine blood pressure fell by 12 +/- 2 (+/- SE) mm Hg with CEI alone, 10 +/- 1 mm Hg with CEI plus P, and 7 +/- 1 mm Hg with CEI plus PI. Active renin rose 8-fold (P less than 0.01), with a peak at 1-2 h, after CEI and 3-fold (P less than 0.02) in response to CEI plus P or CEI plus PI. P did not block the fall in acid-activated inactive renin compared to CEI alone. The nadir of the inactive renin response to both CEI or CEI plus P occurred at 1-2 h. PI, however, prevented the fall in inactive renin. To extend this observation, we compared the effects of infusion of a vasodilator PG (PGA1; 0.6 micrograms/kg X min) and a pure beta-agonist (isoproterenol; 0.3 micrograms/kg X min). PGA1 increased active renin 2.5-fold and decreased inactive renin by 80% (both P less than 0.02), while isoproterenol increased active renin 4.1-fold, but did not significantly change inactive renin. These data suggest that the beta-adrenergic system and PGs at least acutely stimulate renin production at different steps of its biosynthesis or secretion.
Hsueh
W A
WA
Goldstone
R
R
Carlson
E J
EJ
Horton
R
R
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril / Q000494:pharmacology; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007263:Infusions, Parenteral; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012083:Renin / Q000097:blood*
D000806:Angiotensin-Converting Enzyme Inhibitors; D011453:Prostaglandins; D011943:Receptors, Adrenergic, beta; D002216:Captopril; D011433:Propranolol; D012083:Renin; D007545:Isoproterenol; D007052:Ibuprofen; D007213:Indomethacin