Role of nitric oxide in porcine liver circulation under normal and endotoxemic conditions

Abstract

The role of nitric oxide (NO) in the liver vasculature during baseline and endotoxic shock states was evaluated in 17 anesthetized pigs. Mean systemic arterial pressure, pulmonary arterial pressure, and portal venous pressure and flow, hepatic arterial pressure and flow, and cardiac output were measured. Pressure-flow (P-Q) relationships defined resistances as a back pressure and a slope. Inhibition of nitric oxide synthase (NOS) with NG-nitro-L-arginine methyl ester (L-NAME) at baseline increased mean arterial pressure, pulmonary arterial pressure, hepatic arterial pressure, and the slopes of their P-Q relationships (P < 0.05) but had no effect on portal venous pressure or its P-Q relationship. After endotoxin (10 micrograms/kg iv), NO induced arterial dilation and attenuated increases in portal venous and pulmonary arterial resistances (P < 0.05) that were reversed by L-NAME. NOS inhibition was stereospecifically reversed by L-arginine. Local control of liver blood flow at baseline via the hepatic arterial buffer response and hepatic arterial autoregulation were increased in gain after L-NAME. Endotoxic shock ablated the hepatic arterial buffer response and autoregulation independent of either NO or an alpha-adrenergic-receptor agonist (P < 0.05). Under baseline conditions, NO modulates pulmonary, systemic, and hepatic arterial but not portal venous resistances. NO production during endotoxic shock induces arterial hypotension and hepatic arterial vasodilation and attenuates increases in both portal and pulmonary resistances. NOS inhibition in endotoxic shock could increase morbidity due to a loss of local control of liver blood flow and marked increases in resistance to venous return across both the liver and lungs.

Effects of nitric oxide on blood flow distribution and O2extraction capabilities during endotoxic shock

“…Our observations are consistent with a number of recent studies underscoring that NOS inhibitors can significantly exacerbate regional vasoconstriction and ischemia (1,22,23,25,38). In endotoxic rats, Mulder et al (22) demonstrated that NOS inhibition increased organ vascular resistance in the splanchnic vasculature during the first hour of endotoxic shock.…”

“…In endotoxic rats, Mulder et al (22) demonstrated that NOS inhibition increased organ vascular resistance in the splanchnic vasculature during the first hour of endotoxic shock. In endotoxic pigs, Ayuse et al (1) showed that NOS inhibition could alter local control of liver blood flow and markedly increase resistance to venous return across the liver. In endotoxic rabbits, Pastor and Payen (26) reported that N -nitro-Larginine significantly reduced portal vein and hepatic artery blood flows.…”

Nitric oxide in liver injury

“…17 Although it is clear that NO controls basal resistance in the hepatic artery, [18][19][20] a functional role for eNOS in the portal circulation has been more controversial. [21][22][23] By contrast, iNOS is virtually absent in the normal liver but markedly increased in response to inflammation and a variety of oxidative stresses.…”

Protective role of endogenous carbon monoxide in hepatic microcirculatory dysfunction after hemorrhagic shock in rats.

“…Such an NO-mediated vasodilatory action, which involves activation of soluble guanylate cyclase, has been demonstrated in multiple vascular beds (5), including the hepatic circulation (6). While there is only a small (7) or no NO-mediated vasodilatory effect in the hepatic microcirculation under physiologic conditions (8), recent studies have shown that increased generation of NO by either the constitutive (7) or the inducible isoform of NO synthase (iNOS; 8, 9), serves a protective role in minimizing hepatic microcirculatory dysfunction after endotoxemic shock.…”