Atrial natriuretic factor inhibits angiotensin-, norepinephrine-, and potassium-induced vascular contractility.
We have previously shown that the natriuretic effect of rat atrial extract (AE) may be due, perhaps entirely, to its powerful renal hemodynamic actions. The present study was undertaken to test the hypothesis that mammalian atria contain a substance that behaves as a functional antagonist of endogenous vasoconstrictors, by examining the direct effects of AE and extensively purified atrial "natriuretic" factor on the contractile response of rabbit aortic rings to angiotensin II (AII), norepinephrine (NE), and K+-induced depolarization. Dose-response curves to AII and NE (i.e., change in tension vs log hormone concentration) were determined in the absence or presence of boiled AE or ventricular extracts (VE). Increasing concentrations of boiled AE caused a progressive right-ward shift of the AII and NE dose-response curves, whereas VE was without effect. A similar inhibitory effect was produced after extensive purification of atrial natriuretic factor by gel filtration and reversed-phase high performance liquid chromatography (HPLC). It appeared that this factor antagonized AII-induced contractility to a greater degree than that of NE. Moreover, the partially purified factor also inhibited the contraction induced by depolarization with 15 mM KCl in a concentration-dependent manner. These studies show that a substance present in the atria, but not ventricles, blocks both hormone- (receptor) and depolarization- (nonreceptor) induced vasoconstriction in aortic rings. Moreover, this antagonism is retained following extensive purification of an atrial factor that induces natriuresis in the intact rat and isolated rat kidney, suggesting that both the vasoactive and natriuretic properties of AE may reside in a single substance.(ABSTRACT TRUNCATED AT 250 WORDS)
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D016275:Atrial Function; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D045283:Natriuretic Agents; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D011506:Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D014020:Tissue Extracts / Q000494:pharmacology*
D045283:Natriuretic Agents; D011506:Proteins; D014020:Tissue Extracts; D000804:Angiotensin II; D011188:Potassium; D009638:Norepinephrine