Parenteral Na2S, a fast-releasing H2S donor, but not GYY4137, a slow-releasing H2S donor, lowers blood pressure in rats.
Abstract
Hydrogen sulfide (H2S) is involved in blood pressure (BP) regulation. We evaluated hemodynamic effects of Na2S, a fast-releasing H2S donor and GYY4137, a slow-releasing H2S donor. Hemodynamics were recorded in anesthetized Wistar-Kyoto rats at baseline and after intravenous (IV) or intraperitoneal (IP) administration of either a vehicle (20% DMSO) or GYY4137 or Na2S. Stability of GYY4137 in buffers and in plasma was evaluated with nuclear magnetic resonance. The vehicle as well as GYY4137 given IV did not affect mean arterial blood pressure (MABP), whereas Na2S produced a significant decrease in MABP. Similar, IP given Na2S but not GYY4137 lowered MABP. In the buffers at pH of 7.4 and 5.5 and in rat plasma no reaction of GYY4137 was found during 18 hours of observation. In contrast, rapid decomposition of GYY4137 occurred in buffers at pH 2.0. In conclusion, parenteral Na2S but not GYY4137 exerts a hypotensive effect in rats. The lack of hemodynamic effects of GYY4137 may result from its high stability at plasma pH. Since the release of H2S from GYY4137 requires low pH, the biological effects of GYY4137 may be expected in tissues characterized by low pH e.g. in the stomach, and after oral rather than parenteral administration.
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