title: Reduction of plasma renin activity by inhibition of the fatty acid cyclooxygenase in human subjects: independence of sodium retention.
abstract: We carried out the present studies to determine whether the suppression of plasma renin activity (PRA) that follows inhibition of prostaglandin (PG) synthesis can be dissociated from the sodium-retaining effects of these drugs. In an initial investigation we studied the effect of indomethacin on PRA in normal subjects in balance on a 10 mM Na+ diet to prevent Na+ retention. Under these experimental conditions indomethacin did not lower PRA even though the fatty acid cyclooxygenase was inhibited, as indicated by a greater than 70% reduction in the major urinary metabolite of prostaglandin E (PGE-M). Sodium depletion leads to enhanced sympathetic activity. We therefore studied the effect of indomethacin on a group of subjects in 10 mM Na+ balance in whom the effect of increased beta-sympathetic activity was blocked by the administration of propranolol. In this group, indomethacin caused 65% suppression of PGE-M and had no effect on Na+ balance, but reversibly reduced PRA in the supine and upright positions by 84% and 70%, respectively. In normal subjects in 10 mM Na+ balance, the isoproterenol-induced increase in PRA also was unaffected by indomethacin. These data establish that inhibition of the cyclooxygenase can result in a reduction of PRA that is independent of changes in Na+ balance or beta-sympathetic tone.
mesh_terms: D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002986:Clinical Trials as Topic; D003404:Creatinine / Q000652:urine; D016861:Cyclooxygenase Inhibitors; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy; D007213:Indomethacin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D010919:Placebos; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011458:Prostaglandins E / Q000037:antagonists & inhibitors / Q000652:urine; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism; D013268:Stimulation, Chemical
chemical_list: D016861:Cyclooxygenase Inhibitors; D010919:Placebos; D011458:Prostaglandins E; D011943:Receptors, Adrenergic, beta; D000450:Aldosterone; D005665:Furosemide; D012964:Sodium; D011433:Propranolol; D003404:Creatinine; D011451:Prostaglandin-Endoperoxide Synthases; D012083:Renin; D007545:Isoproterenol; D007213:Indomethacin