Colonic hydrogen sulfide produces portal hypertension and systemic hypotension in rats

Hydrogen sulfide, a toxic gas, at low concentrations is also a biological mediator in animals. In the colon, hydrogen sulfide is produced by intestinal tissues and gut sulfur bacteria. Gut-derived molecules undergo liver metabolism. Portal hypertension is one of the most common complications contributing to the high mortality in liver cirrhosis. We hypothesized that the colon-derived hydrogen sulfide may affect portal blood pressure. Sprague-Dawley rats were maintained either on tap water (controls) or on water solution of thioacetamide to produce liver cirrhosis (CRH-R). Hemodynamics were measured after administration of either saline or Na2S, a hydrogen sulfide donor, into (1) the colon, (2) the portal vein, or (3) the femoral vein. Expression of enzymes involved in hydrogen sulfide metabolism was measured by RT-PCR. CRH-R showed a significantly higher portal blood pressure but a lower arterial blood pressure than controls. Saline did not affect hemodynamic parameters. In controls, intracolonic hydrogen sulfide decreased arterial blood pressure and portal blood flow but increased portal blood pressure. Similarly, hydrogen sulfide administered into the portal vein decreased arterial blood pressure but increased portal blood pressure. In contrast, hydrogen sulfide administered into the systemic vein decreased both arterial and portal blood pressures. CRH-R showed significantly greater responses to hydrogen sulfide than controls. CRH-R had a significantly higher liver concentration of hydrogen sulfide but lower expression of rhodanese, an enzyme converting hydrogen sulfide to sulfate. In conclusion, colon-administered hydrogen sulfide increases portal blood pressure while decreasing the systemic arterial blood pressure. The response to hydrogen sulfide is more pronounced in cirrhotic rats which show reduced hydrogen sulfide liver metabolism. Therefore, colon-derived hydrogen sulfide may be involved in the regulation of portal blood pressure, and may contribute to portal hypertension.