Importance of nitric oxide in hepatic arterial blood flow and total hepatic blood volume regulation in pigs

Abstract

The importance of nitric oxide in regulating basal arterial blood flow has been examined in several different vascular beds by intra-arterial infusion of inhibitors of nitric oxide synthesis, but not in the arterial vascular bed of the liver. In the present study, N(G)-nitro-L-arginine (L-NNA), in a dose of 0.5 and 1.0 mumol mL-1 of hepatic arterial blood flow, was infused for 5 min into the hepatic artery in seven pigs anaesthetized with pentobarbital sodium. The haemodynamic effects observed by the first infusion were not further enhanced by the second infusion. Hepatic arterial resistance increased by 143 +/- 38% and hepatic arterial blood flow declined by 38 +/- 10%. A systemic effect due to 'spillover' was observed, as evidenced by an increase in mean aortic blood pressure of 24 +/- 4 mmHg. However, no significant increase in arterial mesenteric resistance was observed and total liver blood flow remained unchanged. Hepatic arterial vasodilation in response to occlusion of the portal vein, the arterial buffer response, remained intact after inhibition of nitric oxide synthesis. Liver lobe thickness, measured by an ultrasonic technique, was not found to change with inhibition of arterial nitric oxide synthesis, excluding a significant direct effect of arterial nitric oxide on liver capacitance. In conclusion, nitric oxide is an important regulator of hepatic arterial resistance, but does not mediate the hepatic arterial buffer response and was not found to play any significant role in total hepatic capacitance regulation.

Impact of intrinsic blood flow regulation in cirrhosis: maintenance of hepatic arterial buffer response

“…HABR has been examined in pigs (1,9), dogs (11), sheep (34), and cats (7,14,15,17,19,22). However, because one of the aims of our study was to set up a cirrhosis model in the rat that allows for measurement of hepatic blood flow, we adopted the technique described by Lautt et al (17) with minor modifications.…”

Effects of Nitric Oxide Donor on Hepatic Arterial Buffer Response in Anesthetized Pigs

“…We have previously found that under anesthesia, local control of hepatic arterial blood flow (Qha) at baseline showed increased gain after NO-synthase (NOS) inhibition, via HABR and autoregulation [6]. Furthermore, Grund et al [9] reported that NO represents an important regulator of Rha but does not mediate the HABR. Since NO normally diminishes autoregulatory control in other organs, inhibition of NOS in the hepatic artery indeed could be expected to increase gain in the HABR.…”

“…However, it has also been suggested that endogenous NO does not mediate the HABR under physiological conditions [6,9]. We have previously found that under anesthesia, local control of hepatic arterial blood flow (Qha) at baseline showed increased gain after NO-synthase (NOS) inhibition, via HABR and autoregulation [6].…”

“…Endogenous nitric oxide (NO) represents an important regulator of hepatic arterial flow [2,[6][7][8][9][10]. However, it has also been suggested that endogenous NO does not mediate the HABR under physiological conditions [6,9].…”

Nitric oxide and liver microcirculation during autoregulation and haemorrhagic shock in rabbit model

“…2 In the liver, NO has already been shown to modify hepatic vascular resistance at the arterial level and in the microcirculation during arterial pressure variations. [3][4][5][6] However, in these studies, the role of NO was estimated by methodologies using cumulative measurements of derived products of NO metabolism or pharmacological inhibition of NO synthases (NOS). This inhibition itself modifies liver blood flow, precluding any evaluation of NO in autoregulation.…”