Na 2 S, a fast-releasing H 2 S donor, given as suppository lowers blood pressure in rats

摘要

Abstract Background Hydrogen sulfide (H 2 S) is involved in blood pressure control. The available slow-releasing H 2 S-donors are poorly soluble in water and their ability to release H 2 S in biologically relevant amounts under physiological conditions is questionable. Therefore, new slow-releasing donors or new experimental approaches to fast-releasing H 2 S donors are needed. Methods Hemodynamics and ECG were recorded in male, anesthetized Wistar Kyoto rats (WKY) and in Spontaneously hypertensive rats (SHR) at baseline and after: 1) intravenous ( iv ) infusion of vehicle or Na 2 S; 2) administration of vehicle suppositories or Na 2 S suppositories. Results Intravenously administered vehicle and vehicle suppositories did not affect mean arterial blood pressure (MABP) and heart rate (HR). Na 2 S administered iv caused a significant, but transient (2–5min) decrease in MABP. Na 2 S suppositories produced a dose-dependent hypotensive response that lasted ～45min in WKY and ～75–80min in SHR. It was accompanied by a decrease in HR in WKY, and an increase in HR in SHR. Na 2 S suppositories did not produce a significant change in corrected QT, an indicator of cardiotoxicity. Na 2 S suppositories increased blood level of thiosulfates, products of H 2 S oxidation. Conclusions Na 2 S administered in suppositories exerts a prolonged hypotensive effect in rats, with no apparent cardiotoxic effect. SHR and WKY differ in hemodynamic response to the H 2 S donor. Suppository formulation of fast-releasing H 2 S donors may be useful in research, if a reference slow-releasing H 2 S donor is not available.