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.
Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovak Republic; Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Lenka
L
Tomasova
Department of Renal and Body Fluid Physiology, M. Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Leszek
L
Dobrowolski
Chair of Medical Biochemistry, Jagiellonian University Medical College, Krakow, Poland.
Halina
H
Jurkowska
Chair of Medical Biochemistry, Jagiellonian University Medical College, Krakow, Poland.
Maria
M
Wróbel
Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.
Tomasz
T
Huc
Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Karol
K
Ondrias
Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw, Poland.
Ryszard
R
Ostaszewski
Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland. Electronic address: mufnal@wum.edu.pl.
Marcin
M
Ufnal
D000285:Administration, Rectal; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D000069196:Gastrointestinal Microbiome; D005905:Glyburide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006862:Hydrogen Sulfide / Q000008:administration & dosage* / Q000494:pharmacology*; D008642:Mesenteric Veins / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar
D005905:Glyburide; D006862:Hydrogen Sulfide
Blood pressure; Gut bacteria; H(2)S; Hypertension; Microbiota