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[The role of nitric oxide in hyperdynamic circulation in portal hypertensive rats]
1Department of Surgery, Renji Hospital, Shanghai Second Medical University, Shanghai 200001.
Objective:
To evaluate the role of nitric oxide (NO) in hyper-hemodynamics in portal hypertension, we investigated the effects of nitric oxide synthase inhibitor L-NMMA with or without L-arginine, the substrate for enzyme NO synthase on the systemic and splanchnic hemodynamics in portal hypertensive rats.
Method:
Ninety-seven male Sprague-Dawley rats were divided into four groups: intrahepatic portal hypertension (IHPH, n = 23) by injection of CCl4, prehepatic portal hypertension (PHPH, n = 26) by stenosis of the portal vein, end-to-side portacaval shunt (PCS, n = 23), and sham-operated controls (SO, n = 25). Animals of each group were divided into three subgroups: systemic administration of L-NMMA (50 mg/kg BW, 1 ml), L-NMMA (50 mg/kg BW, 0.5 ml) plus L-arginine (30 mg/kg BW, 0.5 ml), and normal saline solution (1 ml). The radioactive microsphere method was used for hemodynamic study.
Result:
There was the characteristic of hyperdynamic circulatory state including increased cardiac output and splanchnic blood flow, decreased mean arterial blood pressure, total peripheral vascular resistance and splanchnic vascular resistance in IHPH, PHPH and PCS rats. The hyperdynamic circulatory state in IHPH, PHPH and PCS rats could be effectively reversed by L-NMMA to the resting values of hemodynamics in SO rats, but not the levels after administration of L-NMMA in SO rats, indicating that there is excessive production of NO in portal hypertensive and PCS rats. Administration of L-arginine counterbalanced the effects of L-NMMA on hyperdynamic circulatory state in portal hypertensive and PCS rats.
Conclusion:
NO is an important mediator of hyperdynamic circulation in portal hypertension.