NaS, a fast-releasing HS donor, given as suppository lowers blood pressure in rats.

BACKGROUND

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

RESULTS

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

CONCLUSIONS

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