Parenteral Na ₂ S, a fast-releasing H ₂ S donor, but not GYY4137, a slow-releasing H ₂ S donor, lowers blood pressure in rats

摘要

Hydrogen sulfide (H2S) is involved in blood pressure regulation.We evaluated hemodynamic effects of Na2S andmorpholin-4-ium (4-methoxyphenyl)(morpholino)phosphinodithioate(GYY4137), H2S donors. GYY4137 is themost widely studied slow-releasing H2S donor, however,its ability to release H2S under physiological conditionsis unclear. Hemodynamics were recorded in anaesthetizedWistar-Kyoto rats at baseline and after intravenous(IV) or intraperitoneal (IP) administration of either a vehicle(20% dimethyl sulfoxide), GYY4137 or Na2S. Thestability of GYY4137 in buffers and in plasma was evaluatedwith nuclear magnetic resonance. The vehicle, aswell as GYY4137, given IV did not affect mean arterialblood pressure (MABP), whereas Na2S produced a significantdecrease in MABP. Similarly, IP given Na2S, butnot GYY4137, lowered MABP. In the buffers at pH of 7.4and 5.5 and in rat plasma no reaction of GYY4137 wasfound during 18 hours of observation. In contrast, rapiddecomposition of GYY4137 occurred in buffers at pH2.0. In conclusion, parenteral GYY4137 does not exert ahemodynamic effect in Wistar-Kyoto rats. This seems tobe due to the high stability of GYY4137 at physiologicalpH. Therefore, it is likely that widely reported biologicaleffects of GYY4137 are not H2S-dependent but may dependon GYY4137 itself. However, the H2S-dependentbiological effects of GYY4137 may be expected in tissuescharacterized by low pH.