Role of calcitonin gene-related peptide in the vascular system on the development of the hyperdynamic circulation in conscious cirrhotic rats

Abstract

Background/Aims: Calcitonin gene-related peptide (CGRP), a potent vasodilator, plays an important role in modulating vascular tone, acting as a noncholinergic nonadrenegic neurotransmitter. The aim of this study was to assess the role of CGRP, present in the vascular system, in the developent of the hyperdynamic circulation observed in liver cirrhosis. Methods: Two does of human α-CGRP [8–37], a specific antagonist of CGRP, were administered to cirrhotic and control rats. Hemodynamics were evaluated using radioactive microspheres in conscious animals. To investigate the arterial depressor effect of exogenous CGRP, we constructed a dose-response curve for mean arterial pressure in cirrhotic and control rats by administering human α-CGRP. Results: The administration of high-dose human α-CGRP [8–37] (300 nmol · kg body weight −1 · min −1) significantly increased both the mean arterial pressure (21±2 vs. 13±1%, p<0.01) and total vascular resistance (76±5 vs. 54±5%, p<0.01) in cirrhotic rats, compared to control rats. The splanchnic hemodynamic effects induced by human α-CGRP [8–37] were a significant decrease in percent change of portal venous inflow −42±3 vs −33±3%, p<0.05) and a significant increase in percent change of splanchnic arterial resistance (110±9 vs 76±55, p<0.01) in cirrhotic rats, compared to control rats. Low-dose human α-CGRP [8–37] (60 nmol · kg body weight −1 · min −1) caused was much less than for the high-dose administration. The vascular response to human α-CGRP was significantly reduced in cirrhotic rats as compared to controls (ANOVA, p<0.01). Plasma concentrations of CGRP were significantly elevated in cirrhotic rats. Conclusions: CGRP in the vascular system was involved in the modulation of vasodilation in rats with liver cirrhosis, as demonstrated by the administration of a selective CGRP antagonist and exogenous CGRP.