Na2S, a fast-releasing H2S donor, given as suppository lowers blood pressure in rats

Abstract

Background: Hydrogen sulfide (H₂S) is involved in blood pressure control. The available slow-releasing H₂S-donors are poorly soluble in water and their ability to release H₂S in biologically relevant amounts under physiological conditions is questionable. Therefore, new slow-releasing donors or new experimental approaches to fast-releasing H₂S 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 Na₂S; 2) administration of vehicle suppositories or Na₂S suppositories.

Results: Intravenously administered vehicle and vehicle suppositories did not affect mean arterial blood pressure (MABP) and heart rate (HR). Na₂S administered iv caused a significant, but transient (2-5min) decrease in MABP. Na₂S 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. Na₂S suppositories did not produce a significant change in corrected QT, an indicator of cardiotoxicity. Na₂S suppositories increased blood level of thiosulfates, products of H₂S oxidation.

Conclusions: Na₂S administered in suppositories exerts a prolonged hypotensive effect in rats, with no apparent cardiotoxic effect. SHR and WKY differ in hemodynamic response to the H₂S donor. Suppository formulation of fast-releasing H₂S donors may be useful in research, if a reference slow-releasing H₂S donor is not available.

Keywords: H(2)S donor; Hydrogen sulphide; Hypertension; Suppositories; Thiosulfates.