Intracolonic hydrogen sulfide lowers blood pressure in rats.

Research suggests that hydrogen sulfide (HS) is an important biological mediator involved in various physiological processes including the regulation of arterial blood pressure (BP). Although HS is abundant in the colon, the effects of gut-derived HS on the circulatory system have not yet been investigated. We studied the effects of intracolonic administration of NaS, a HS 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 NaS·9HO saline solution at a dose range of 10-300 mg/kg of BW. The HS 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 NaS-induced decrease in MABP was reduced by pretreatment with glibenclamide, an inhibitor of ATP-sensitive potassium-channels. NaS did not affect mesenteric vein blood flow. Rats treated with NaS showed increased portal blood levels of thiosulfate and sulfane sulfur, products of HS 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 NaS. The HS donor decreased heart rate but did not affect ECG morphology and QTc interval. In conclusion the gut-derived HS may contribute to the control of BP and may be one of the links between gut microbiota and hypertension. Furthermore, gut-derived HS may be a therapeutic target in hypertension.