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

Abstract

Background. Direct evidence of nitric oxide (NO) involvement in the regulation of hepatic microcirculation is not yet available under physiological conditions nor in haemorrhagic shock. Methods. A laser Doppler flowmetry was used to measure liver perfusion index and a specific NO-sensitive electrode was inserted into liver parenchyma of anaesthetized rabbits. Hepatic autoregulation during moderate hypovolaemia {mean arterial pressure at 50 mm Hg without liver perfusion alteration; blood withdrawal 17.7 (4.2) ml [mean (SD)]} or haemorrhagic shock [mean arterial pressure at 20 mm Hg associated with liver perfusion impairment and lactic acidosis; blood withdrawal 56.0 (6.8) ml] were investigated over 60 min and were followed by a rapid infusion of the shed blood. Involvement of NO synthases was evaluated using a non-specific inhibitor, NAPNA (Nv-nitro-L-arginine P-nitro-anilide). Results. In the autoregulation group, a decrease [30.0 (4.0) mm Hg] of mean arterial pressure did not alter liver perfusion index, whereas the liver NO concentration increased and reached a plateau [125 (10)%; compared with baseline; P<0.05]. This NO concentration was reduced to zero by the administration of NO synthase inhibitor. Haemorrhagic shock led to a rapid decrease in liver perfusion index [60 (7)%; compared with baseline; P<0.05] before an immediate and continuous increase in NO concentration [250 (50)%; compared with baseline; P<0.05]. Infusion of NO inhibitor before haemorrhagic shock reduced the NO concentration to zero and hepatic perfusion by 60 (8)% (P<0.05) of the baseline. Mean arterial pressure increased simultaneously. In these animals, during haemorrhage, a continuous increase in NO concentration still occurred and liver perfusion slightly increased. In all groups but NAPNA+haemorrhagic shock, blood replacement induced recovery of baseline values. Conclusions. NO plays a physiological role in the liver microcirculation during autoregulation. Its production is enzyme-dependent. Conversely, haemorrhagic shock induces a rapid increase in hepatic NO that is at least partially enzyme-independent.

Effect of ketamine on oxidative stress following lipopolysaccharide administration

“…Reduced glutathione is increased and nitric oxide levels decreased following the administration of antidepressant drugs. In the liver, nitric oxide is involved in regulation of hepatic haemodynamics (Mittal et al, 1994[ 46 ]; Lhuillier et al, 2006[ 41 ]) and in hepatic regeneration (Tuncyurek et al, 2006[ 67 ]). Studies indicated that inhibition of nitric oxide synthase increased hepatic lipid peroxidation, serum liver enzymes and bilirubin in CCl 4 -intoxicated rats (Muriel, 1998[ 51 ]), while increasing nitric oxide availability with L-arginine improved hepatic arterial and portal blood flow and sinusoidal oxygenation in experimental hepatic steatosis (Ijaz et al, 2005[ 30 ]).…”

Profile of hemodynamic and gasometric parameters in rabbits submitted to controlled hemorrhagic shock

“…For instance, Girisgin et al 10 , using a experimental model in rabbits, studied importance of early and effective fluid resuscitation in hypovolemic shock treatment with the utilization of fluid replacement via the rectum, as a possible lifesaving method in situations where veins cannot be accessed quickly. Lhuillier et al 11 , also with a rabbit model, evaluate the nitric oxide involvement in the regulation of hepatic microcirculation under physiological conditions and in hemorrhagic shock, and concluded that it plays a important role in the autoregulation of liver microcirculation during the hemorrhagic shock. In the same manner, Komori et al 12 , studied the effects of hydroxyethyl starch on the microcirculation, hemodynamics, and colloidal osmotic pressure in a rabbit model of hemorrhagic shock, and verified that intravenous infusion of this solution effectively maintains these parameters during acute severe hemorrhage.…”

Hepatoprotective effects of the nitric oxide donor isosorbide-5-mononitrate alone and in combination with the natural hepatoprotectant, silymarin, on carbon tetrachloride-induced hepatic injury in rats

“…In liver sinusoids, specialized contractile endothelial cells exist which may be involved in the local control of haemodynamics and which are sensitive to vasoactive agents (Bani et al 2001). Nitric oxide is involved in the modulation of hepatic microcirculatory perfusion (Li et al 2003;Lhuillier et al 2006) and increasing hepatic bioavailability of nitric oxide has been shown to protect against experimental liver injury. In this context, in rats treated with CCl 4 , inhibition of nitric oxide synthase resulted in increased hepatic lipid peroxidation, serum liver enzymes and bilirubin (Muriel 1998), whereas the administration of L-arginine improved hepatic arterial and portal blood flow and sinusoidal oxygenation in experimental hepatic steatosis (Ijaz et al 2005).…”