Influence of atrial natriuretic factor on 5-(N-ethyl-N-isopropyl)amiloride-sensitive 22Na+ uptake in rabbit aorta.
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.
Gupta
S
S
Section of Pharmacology, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, Massachusetts.
Cragoe
E J
EJ
Deth
R C
RC
D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D006152:Cyclic GMP / Q000096:biosynthesis; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011817:Rabbits; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects
D011956:Receptors, Cell Surface; D009599:Nitroprusside; D015240:Phorbol 12,13-Dibutyrate; D000584:Amiloride; D009320:Atrial Natriuretic Factor; D012964:Sodium; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP; C039614:ethylisopropylamiloride