The bradykinin B 2 receptor antagonist Icatibant (HOE 140) corrects avid Na + retention in rats with CCl 4-induced liver cirrhosis: possible role of enhanced microvascular leakage

Abstract

Avid Na + retention is a hallmark of liver cirrhosis. The aim of this study was to investigate whether and how bradykinin is involved in Na + retention in rats with CCl 4-induced liver cirrhosis. To this end the bradykinin B 2 receptor antagonist Icatibant (HOE 140) was used. On one hand, bradykinin has a renal natriuretic action. On the other hand, bradykinin is a potent mediator of both vasodilation and microvascular leakage. Both vascular mechanisms, which are reported for cirrhosis, could cause vascular underfilling and Na + retention by activating the renin–angiotensin–aldosterone system. Icatibant normalised Na + retention and reduced the hyperactivity of the renin–angiotensin–aldosterone system, suggesting a bradykinin-induced vascular disturbance. Icatibant had no significant effect on the mild hypotension which developed with CCl 4 treatment. However, there was indirect evidence for enhanced microvascular leakage that was strongly inhibited by Icatibant. Our experimental results demonstrate that bradykinin is a key mediator of Na + retention in liver cirrhosis and suggest that a bradykinin-induced increase in microvascular leakage is mainly responsible.