PROLONGED ANTAGONISM OF ALPHA(1)-ADRENERGIC VASOCONSTRICTION IN THE RAT-LIVER BY ATRIAL-NATRIURETIC-PEPTIDE

Background/Aims: Vasodilator hormones that regulate hepatic circulatio n at physiological concentrations have not been sufficiently identifie d. The presence of atrial natriuretic peptide (ANP) and its receptors in the hepatic vascular bed suggest such vasorelaxing potential. Metho ds: Livers of male Sprague-Dawley rats were perfused in a flow-constan t fashion. The selective alpha(1)-adrenergic agonist phenylephrine (PE ) (1.5 mu mol/L) was infused from 30 to 36 minutes and again from 70 t o 76 minutes after starting perfusion (n = 5). ANP (0.1 pmol/L to 200 nmol/L), des-(Gln(18), Ser(19), Gly(20), Leu(21), Gly(22))-ANP fragmen t (C-ANP) (20 nmol/L), or (8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) (50 mu mol/L) (each n = 4) were added from 20 to 40 minut es. Results: During the first infusion of PE, portal pressure increase d from 3.7 +/- 0.5 to 12.1 +/- 0.8 cm H2O maximally (mean +/- SD) and increased again to 11.5 +/- 2.0 during the second PE infusion. ANP at physiological concentrations reduced both PE-induced increases of port al pressure in a dose-dependent fashion, reaching half-maximal effects around 20 pmol/L and maximal effects (about 50% inhibition of PE-indu ced vasoconstriction) at 40 pmol/L. The cGMP analogue 8-Br-cGMP showed the same long-lasting vasodilating effect as ANP. In contrast, C-ANP, which binds only to the ANP C-receptor, had no effects. Conclusions: Physiological concentrations of ANP antagonize alpha(1)-adrenergic vas oconstriction in the liver, suggesting an important function in the hu moral regulation of hepatic circulation. The prolonged hemodynamic eff ect of ANP seems to be ANP A-receptor/guanylyl cyclase/cGMP-mediated.