Nitric oxide mediates hepatic arterial vascular escape from norepinephrine-induced constriction

Abstract

The involvement of nitric oxide (NO) in the vascular escape from norepinephrine (NE)-induced vasoconstriction was investigated in the hepatic arterial vasculature of anesthetized cats. The hepatic artery was perfused by free blood flow or pump-controlled constant-flow, and NE (0.15 and 0.3 microg x kg(-1) x min(-1), respectively) was infused through the portal vein. In the free-flow perfusion model, the NE-induced hepatic vasoconstriction recovered from the maximum point of the constriction, resulting in 36.6 +/- 5. 9% vascular escape. Blockade of NO formation with N(omega)-nitro-L-arginine methyl ester (L-NAME, 2.5 mg/kg ipv) potentiated NE-induced maximum vasoconstriction, and the potentiation was reversed by L-arginine (75 mg/kg ipv). Furthermore, NE-induced vasoconstriction became more stable after L-NAME, resulting in an inhibition of vascular escape (7.5 +/- 3.3%), and the inhibition was reversed by L-arginine (23.0 +/- 6.4%). Similar potentiation of NE-induced vasoconstriction and inhibition of hepatic vascular escape by L-NAME (40.4 +/- 4.3% control vs. 10.2 +/- 3.7% post-L-NAME escape) and the reversal by L-arginine were also observed in the constant-flow perfusion model. The data suggest that NO is the major endogenous mediator involved in the hepatic vascular escape from NE-induced vasoconstriction.

Perfusion CT Assessment of Tissue Hemodynamics Following Hepatic Arterial Infusion of Increasing Doses of Angiotensin II in a Rabbit Liver Tumor Model

“…These results suggest that the 2.5 m g/mL dose of angiotensin II can cause vasoconstriction in the adjacent and distant normal liver that is suffi cient to decrease the BF and BV in these regions without invoking the hepatic arterial buffer response ( 30 ) or inducing hepatic arterial vascular escape ( 31 ), which cause arterial vasodilatation in the normal liver parenchyma that is mediated by increased local levels of adenosine and nitric oxide, respectively. The combination of these two hepatic refl ex responses has been shown to give the normal liver the unique ability to escape from severe vasoconstrictive infl uences ( 30,31 ); this appears to have occurred at the higher angiotensin II doses, especially 50.0 m g/mL, in our study. Furthermore, only at the 2.5 m g/mL dose was the capillary permeabilitysurface area product of the tumor signifi cantly higher than that of the surrounding normal liver tissue.…”

Hypoxic hepatitis – epidemiology, pathophysiology and clinical management

“…Other mediators involved in regulatory processes of mesenteric and hepatic blood fl ow are norepinephrine, epinephrine, agents originating from the renin-angiotensin-aldosterone sytem, endothelins and nitric oxide (see Disturbances in mesenteric blood distribution during critical illness below) [47][48][49][50].…”

“…Nitric oxide attenuates experimental norepinephrineinduced vasoconstriction [49]. A recent clinical study demonstrated that inhaled nitric oxide reduced reperfusion-induced hepatic cell death and improved liver function tests in patients undergoing liver transplantation [54].…”

The paradox of nitric oxide in cirrhosis and portal hypertension: Too much, not enough

“…17 This demonstration of the essential functional role of NO in the regulation of the IHVR was confirmed later in different species and using different experimental approaches. 18,19 Using the classical method of the hepatic venous wedged pressure to measure liver sinusoidal pressure in the isolated perfused liver, we determined that in normal rat liver NO modulates sinusoidal and presinusoidal resistance whereas in the cirrhotic liver NO has a predominant sinusoidal effect. 20,21 Recent studies investigated the enzymatic origin of this NO production in the liver.…”