Intracolonic hydrogen sulfide lowers blood pressure in rats

Research suggests that hydrogen sulfide (H₂S) is an important biological mediator involved in various physiological processes including the regulation of arterial blood pressure (BP). Although H₂S is abundant in the colon, the effects of gut-derived H₂S on the circulatory system have not yet been investigated. We studied the effects of intracolonic administration of Na₂S, a H₂S donor, on systemic hemodynamics. Hemodynamics were recorded in anesthetized, normotensive Wistar Kyoto and spontaneously hypertensive rats at baseline and after intracolonic injection of either saline (controls) or Na₂S·9H₂O saline solution at a dose range of 10-300 mg/kg of BW. The H₂S donor produced a significant, dose-dependent decrease in mean arterial blood pressure (MABP), which lasted several times longer than previously reported after parenteral infusions (>90 min). The effect was more pronounced in hypertensive than in normotensive rats. The Na₂S-induced decrease in MABP was reduced by pretreatment with glibenclamide, an inhibitor of ATP-sensitive potassium-channels. Na₂S did not affect mesenteric vein blood flow. Rats treated with Na₂S showed increased portal blood levels of thiosulfate and sulfane sulfur, products of H₂S oxidation. In contrast, rats treated with neomycin, an antibiotic, showed significantly decreased levels of thiosulfate and sulfane sulfur, and a tendency for greater hypotensive response to Na₂S. The H₂S donor decreased heart rate but did not affect ECG morphology and QTc interval. In conclusion the gut-derived H₂S may contribute to the control of BP and may be one of the links between gut microbiota and hypertension. Furthermore, gut-derived H₂S may be a therapeutic target in hypertension.