Hemodynamic Actions of a Synthetic Atrial Natriuretic Factor

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Abstract
Summary: The recently discovered atrial natriuretic factor (ANF), as well as synthetic ANF, has been demonstrated to produce diuresis and vasodilation. However, the vascular actions appear to be selective. In view of this apparent relative specificity, the hemodynamic actions of synthetic ANF (atriopeptin II, 23 amino acid rat sequence) were examined in intact animals and in vascular beds as well as in isolated cardiac preparations. Administration of 1–100 μg/kg of ANF i.v. into conscious spontaneously hypertensive rats (SHRs) resulted in a dose-related fall in blood pressure. Heart rate decreased at the lowest dose. Cardiac output was depressed. Infusion of 1 μg/kg/min also reduced blood pressure and decreased cardiac output slightly (15%). Intra-arterial (i.a.) administration or i.v. injection of ANF into the blood supply of a kidney of anesthetized SHRs augmented renal blood flow and reduced renal vascular resistance. In contrast, i.a. administration into the hind-quarters failed to increase blood flow or decrease resistance of this bed significantly. The specific dopamine1 (DA1)-receptor agonist SKF 82526 was examined for comparative purposes and was found to augment both renal and hindquarter blood flow following i.a. administration. The renal vasodilator actions of SKF 82526 but not ANF were antagonized by the specific DA1-receptor blocker SCH 23390 (hindquarter effects were not evaluated). ANF did not affect the force of contraction or rate of beating of isolated guinea pig atria or isolated hearts and therefore does not appear to possess direct inotropic or chronotropic properties. In conclusion, ANF lowered blood pressure in conscious SHRs; the lowering of pressure was accompanied by a slight fall in cardiac output, but there was no reflex tachycardia. The renal dilation probably contributed to the hypotensive response. The vascular actions of ANF appear to be selective in vivo as in vitro.