Analysis of Decreases in Systemic Arterial Pressure and Heart Rate in Response to the Hydrogen Sulfide Donor Sodium Sulfide.

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 current study is 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 (iv) administration of the H2S donor sodium sulfide (Na2S) in the anesthetized Sprague-Dawley (SD) 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 the PR or QTc(n)-B intervals. In experiments where respiration was maintained with a mechanical ventilator, we observed that 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. Co-administration of glybenclamide significantly increased MAP and HR responses at some doses, but methylene blue, diltiazem, and ivabradine had no significant effect when compared to control. The decreases in MAP and HR in response to Na2S can be dissociated and are independent of changes in respiratory function, K(+)ATP channels, methylene blue-sensitive mechanism involving L-type voltage sensitive calcium channels, or hyperpolarization-activated cyclic nucleotide-gated channel (HCN) If channels. Cardiovascular responses observed in spontaneously hypertensive (SHR) rats were more robust than those in SD rats.