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Na 2 S, a Fast‐Releasing H 2 S Donor, Given as Suppository but not Parenteral GYY4137, a Slow‐Releasing H 2 S Donor, Lowers Blood Pressure in Rats
Author(s) -
Ufnal Marcin,
Tomasova Lenka,
Drapala Adrian,
Koszlewski Dominik,
Ostaszewski Ryszard
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb644
Subject(s) - suppository , chemistry , hemodynamics , blood pressure , pharmacology , anesthesia , medicine
Objectives Although several H 2 S donors are available, their usefulness in research is questionable. Here, we evaluated hemodynamic effects of Na 2 S, a fast‐releasing H 2 S donor and GYY4137, a slow‐releasing H 2 S donor. Methods Hemodynamics were recorded in anesthetized Wistar Kyoto rats (WKY) and Spontaneously hypertensive rats (SHR) at baseline and after: 1) intraperitoneal (i.p.) infusion of either a vehicle (20% DMSO) or GYY4137 or Na 2 S; 2) intravenous (i.v.) infusion of either the vehicle or GYY4137 or Na 2 S; 3) per rectal administration of vehicle suppositories or suppositories with Na 2 S. Stability of GYY4137 in buffers and in rat plasma was evaluated with NMR. Results The vehicle and GYY4137 given i.p. and i.v. did not affect mean arterial blood pressure (MABP), whereas Na 2 S produced a significant, but transient (2–5 min) decrease in MABP. Administration of Na 2 S suppositories produced a dose dependent hypotensive response that lasted 60–90 min in WKY and SHR. 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. Conclusions Na 2 S given in suppositories exerts a prolonged hypotensive effect in rats. GYY4137 does not affect MABP in rats, which seems to result from its high stability at physiological pH. Suppository formulation of fast‐releasing H 2 S donors may be useful in basic research as long as a reference slow‐releasing H 2 S donor is not available. Support or Funding Information This study was supported by The National Science Centre, Poland grant No. 2016/22/E/NZ5/00647