Analysis of decreases in systemic arterial pressure and heart rate in response to the hydrogen sulfide donor sodium sulfide

Abstract

The actions of hydrogen sulfide (H₂S) on the heart and vasculature have been extensively reported. However, the mechanisms underlying the effects of H₂S are unclear in the anesthetized rat. The objective of the present study was to investigate the effect of H₂S on the electrocardiogram and examine the relationship between H₂S-induced changes in heart rate (HR), mean arterial pressure (MAP), and respiratory function. Intravenous administration of the H₂S donor Na₂S in the anesthetized Sprague-Dawley rat decreased MAP and HR and produced changes in respiratory function. The administration of Na₂S significantly increased the RR interval at some doses but had no effect on PR or corrected QT(n)-B intervals. In experiments where respiration was maintained with a mechanical ventilator, we observed that Na₂S-induced decreases in MAP and HR were independent of respiration. In experiments where respiration was maintained by mechanical ventilation and HR was maintained by cardiac pacing, Na₂S-induced changes in MAP were not significantly altered, whereas changes in HR were abolished. Coadministration of glybenclamide significantly increased MAP and HR responses at some doses, but methylene blue, diltiazem, and ivabradine had no significant effect compared with control. The decreases in MAP and HR in response to Na₂S could be dissociated and were independent of changes in respiratory function, ATP-sensitive K⁺ channels, methylene blue-sensitive mechanism involving L-type voltage-sensitive Ca²⁺ channels, or hyperpolarization-activated cyclic nucleotide-gated channels. Cardiovascular responses observed in spontaneously hypertensive rats were more robust than those in Sprague-Dawley rats.NEW & NOTEWORTHY H₂S is a gasotransmitter capable of producing a decrease in mean arterial pressure and heart rate. The hypotensive and bradycardic effects of H₂S can be dissociated, as shown with cardiac pacing experiments. Responses were not blocked by diltiazem, ivabradine, methylene blue, or glybenclamide.

Keywords: ATP-sensitive potassium channels; H2S donors; L-type calcium channels; bradycardia; hypotension.