Converting enzyme inhibition augments and competitive inhibition of angiotensin II partially restores reflex adrenal catecholamine release in anephric dogs.
Adrenal epinephrine (E) release after hemorrhage in anesthetized dogs is blunted by acute nephrectomy and restored by angiotensin II infusion. In the present study, we report the effect of converting enzyme inhibition by SQ 20881, a decapeptide, and of competition inhibition of angiotensin II by saralasin (1-Sar-8-Ala-Ang-II) on reflexly stimulated adrenal release of E and norepinephrine (NE) in three groups of acutely anephric dogs. Aortic catheters and adrenal vein to femoral vein Silastic shunts were placed in dogs anesthetized with pentobarbital and mechanically ventilated. Adrenal secretion rates were calculated from adrenal vein to aorta catecholamine concentration differences divided by measured adrenal venous flow. Catecholamine concentrations were determined with trihydroxyindole technique. Blood samples were obtained before and 15, 30, and 60 min after rapid hemorrhage to a stable mean arterial pressure of 50 mm Hg. Saralasin infusion (10 microgram/kg/min) supported adrenal E release in anephric hemorrhaged dogs toward secretion rates comparable to those seen in intact dogs. Anephric SQ 20881 (approximately 0.5 microgram/kg) recipients had delayed (60 min) augmented adrenal E and NE release after hemorrhage. In resting animals not reflexly stimulated by hypovolemia, neither drug provoked adrenal E or NE release. These results suggest an agonist effect of saralasin on reflex adrenal E release and increased responsiveness of the stimulated adrenal medulla under the influence of converting enzyme inhibition.
D000313:Adrenal Medulla / Q000378:metabolism*; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D004285:Dogs; D004837:Epinephrine / Q000378:metabolism*; D006470:Hemorrhage / Q000503:physiopathology; D007668:Kidney / Q000502:physiology*; D009392:Nephrectomy; D012018:Reflex; D012504:Saralasin / Q000494:pharmacology; D013722:Teprotide / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D013722:Teprotide; D012504:Saralasin; D004837:Epinephrine