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Influence of atrial natriuretic factor on 5-(N-ethyl-N- isopropyl)amiloride-sensitive 22Na+ uptake in rabbit aorta

S Gupta, EJ Cragoe and RC Deth

Section of Pharmacology, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, Massachusetts.

Because atrial natriuretic factor (Atriopeptin II, ANF) exerts potent effects on Na+ transport in a number of tissues, we examined its influence on 22Na+-uptake in isolated rabbit aorta segments and the possible relation to ANF-induced vasorelaxation. ANF increased 22Na+- uptake by 44% with an EC50 of 12 nM whereas sodium nitroprusside was without effect. The increase was blocked by the selective inhibitor of Na+/H+ exchange 5-(N-ethyl-N-isopropyl)amiloride (EIPA) but was not sensitive to the guanylate cyclase inhibitor LY 83583, indicating ANF- induced activation of Na+/H+ exchange via a cyclic GMP (cGMP) independent pathway. The ability of ANF to relax phenylephrine-induced contractions of rabbit aorta was inhibited by EIPA at concentrations which produced inhibition of Na+/H+ exchange whereas sodium nitroprusside-induced relaxation was only marginally affected. EIPA caused a 90% decrease in the ability of ANF to increase cGMP, but did not interfere with the sodium nitroprusside-induced increase. LY 83583 blocked the ability of ANF to increase cGMP formation but failed to reduce ANF-induced vasorelaxation. These results suggest that ANF activation of EIPA-sensitive 22Na+-uptake occurs before cGMP formation perhaps at the level of the ANF receptor itself. The vasorelaxant effects of ANF involve a significant cGMP-independent component which is EIPA sensitive.

Volume 248, Issue 3, pp. 991-996, 03/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics




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