Effects of indomethacin and meclofenamate on renin release and renal hemodynamic function during chronic sodium depletion in conscious dogs.
We studied the control of renin release and renal hemodynamic function by administering prostaglandin synthetase inhibitors to conscious sodium-depleted dogs with blockade of the adrenergic nervous system induced by bilateral renal denervation and propranolol administration. Indomethacin (10 mg/kg) reduced plasma renin activity (PRA) by 59% from a high sodium-depleted value, but PRA was still 3 times the normal sodium-repleted level. Arterial pressure, CCr, CPAH, urine flow, and potassium excretion fell strikingly. Similar results were obtained with meclofenamate. When SQ 14,225 was given to another group of conscious, sodium-depleted dogs with adrenergic nervous system blockade, PRA increased from the high sodium-depleted level of 5.7 to 29.3 ng of Angiotensin I (AI)/ml per hour; indomethacin (10 mg/kg) appeared to reduce PRA (0.05 less than P less than 0.1) but to only 12.1 ng of AI/ ml per hour, which is 17 times the normal level. This high level of PRA after blockade of the adrenergic nervous system and injection of indomethacin suggests that important mechanisms other than norepinephrine and renal prostaglandins control renin release; it is proposed that both the renal vascular receptor and the macula densa are involved. The marked decreases in CCr and CPAH in response to indomethacin emphasize the important role of renal prostaglandins in the control of renal hemodynamic function during sodium depletion.
D000818:Animals; D002216:Captopril / Q000008:administration & dosage; D004285:Dogs; D005260:Female; D006439:Hemodynamics; D007213:Indomethacin / Q000494:pharmacology*; D007668:Kidney / Q000294:innervation; D007677:Kidney Function Tests; D008469:Meclofenamic Acid / Q000494:pharmacology*; D011433:Propranolol / Q000008:administration & dosage; D012083:Renin / Q000097:blood*; D012964:Sodium / Q000172:deficiency; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D062367:ortho-Aminobenzoates; D008469:Meclofenamic Acid; D002216:Captopril; D012964:Sodium; D011433:Propranolol; D012083:Renin; D007213:Indomethacin