Hyperkinetic circulation and decreased sensitivity to vasoconstrictors following portacaval shunt in the rat. Effects of chronic nitric oxide inhibition

Background/Aims: This study aimed to investigate: (i) whether the hyperkine tic circulation that develops after portacaval shunt is associated with dec reased vascular sensitivity to vasoconstrictors and (ii) the role of nitric oxide on its pathogenesis, Methods: Portacaval-shunted and sham-operated rats received long-term treat ment with the nitric oxide inhibitor L-NAME (osmotic minipump) or its inact ive enantiomer D-NAME. Measurements of arterial pressure, cardiac output an d superior mesenteric artery blood flow (transit-time flow probe) were done 4 days later in baseline conditions and after increasing doses of methoxam ine. Peripheral and superior mesenteric vascular resistance were calculated . Results: Portacaval shunted rats showed a significantly lower peripheral an d superior mesenteric vascular resistance and a significant reduction in th eir response to incremental doses of methoxamine than sham-operated control s. Chronic nitric oxide inhibition attenuated the systemic but not the spla nchnic vasodilatation and totally corrected the hyposensitivity to methoxam ine of portacaval-shunted rats. However, they still had a significantly low er peripheral and superior mesenteric vascular resistance than sham-operate d rats. Conclusions: This study shows that the splanchnic and systemic hyporesponsi veness to methoxamine observed in portacaval-shunted rats could be explaine d by an excess of nitric oxide. However, other factors may be involved in m aintaining splanchnic and systemic vasodilatation despite NO-inhibition.