The NO Donor Sodium Nitroprusside Reverses the Negative Effects on Hepatic Arterial Flow Induced by Endotoxin and the NO Synthase Inhibitor L-NAME

Abstract

In previous studies we have observed that the nitric oxide synthase inhibitor L-NAME induces a profound deterioration of liver circulation in experimental endotoxemia. Using the same porcine model we now have evaluated the possibility of modulating these effects with the nitric oxide donor sodium nitroprusside. Infusion of endotoxin led to a gradual deterioration of hemodynamic parameters, including liver blood flow. The decreases in portal blood flow paralleled and matched the decreases in cardiac output, and no compensatory increase in hepatic arterial flow occurred. L-NAME had detrimental effects on hemodynamics, including the liver circulation. The latter effects could, however, partially be reversed by sodium nitroprusside. Hepatic arterial flow increased from 1.9 to 7.2 ml/kg/min, with a concomitant decrease in hepatic arterial resistance from 5,364 to 1,746 dyn s/cm5 kg. A control group exhibited no significant change in either flow or resistance. The response to sodium nitroprusside was rapid and vigorous, and probably largely due to relaxation of the hepatic arterioles, and not to abatement of intrahepatic edema or plugging of the sinusoids. Furthermore, we conclude that the endotoxin-induced dysfunction of the hepatic arterial buffer response may be due to a selective inhibition of vascular endothelial function.

Regulation of hepatic blood flow: The hepatic arterial buffer response revisited

“…While nitric oxide induces arterial hypotension and hepatic arterial vasodilation during endotoxic shock [85] , ablation of the HABR has been shown to be independent of nitric oxide or an α-adrenergic-receptor agonist [84] . On the contrary, early administration of the nitric oxide donor sodium nitroprusside can reverse the negative effects on hepatic arterial flow induced by endotoxin [86,87] . Moreover, sodium nitroprusside partially reverses the detrimental effect of the nitric oxide synthase inhibitor L-NAME in experimental endotoxemia, which implies that the endotoxin-induced dysfunction of the HABR may be due to a selective inhibition of vascular endothelial function [87] .…”

The Hepatic Microcirculation: Mechanistic Contributions and Therapeutic Targets in Liver Injury and Repair

“…In addition to physiological conditions, the HABR has been described to be also maintained in cirrhotic livers of animals and humans (18,572,670) and after liver transplantation (286). Of interest, this response is lost upon brain death (236), under increased intraabdominal pressure (CO 2 pneumoperitoneum) (671), and during endotoxemia (25,262,708). The fact that NO (262,789) but also terlipressin (24) restore the HABR during endotoxemia reflects the temporal and spatial complexity in the misbalance of expression of vasoconstrictive and vasodilative mediators (see sect.…”

Opening the microcirculation: can vasodilators be useful in sepsis?

“…The NO donor sodium nitroprusside has been shown in sepsis to improve both liver microvascular flow (measured by intravital microscopy) and organ function when given early during endotoxemia in rats [60]. In recent studies we investigated the efficacy of the NO donor SIN-1 and dopexamine in resuscitating microvascular oxygenation of the intestines in endotoxic pigs [11,61].…”