Haemodynamic responses to a ring-deleted analogue of atrial natriuretic peptide in rats with cirrhosis.

Abstract

In cirrhosis, the effects of selective activation of atrial natriuretic peptide (ANP) R2-receptors on haemodynamics, endogenous ANP (ANP1-28) and sodium excretion are unknown. The aim of the present study was to examine the effects of selective activation of ANP-R2 receptors by ANP4-23 (a ring-deleted analogue of endogenous ANP) on haemodynamics, plasma ANP1-28 concentrations and urinary sodium excretion in conscious cirrhotic and normal rats. Haemodynamics and sodium excretion were measured prior to and following administration of ANP4 23. Plasma ANP1-28 concentrations were also measured. In cirrhotic rats, ANP4-23 significantly decreased portal pressure and tributary blood flow by 15% and 25% respectively but significantly increased portal territory vascular resistance by 30%. Systemic and renal haemodynamics were not altered by ANP4-23. In normal rats, ANP4-23 did not significantly change splanchnic, renal and systemic haemodynamics. In both groups of rats, ANP4-23 increased plasma ANP1-28 concentrations but did not change sodium excretion. ANP4-23 administration induced splanchnic vasoconstriction in cirrhotic but not in normal rats. ANP4-23-elicited vasoconstriction caused a portal hypotensive effect in cirrhotic rats. Finally, in both groups, ANP4-23 caused an increase in plasma ANP1-28 concentrations but did not increase sodium excretion.