Abstract
The actions of hydrogen sulfide (H(2)S) on the heart and vasculature have been extensively reported. However, the mechanisms underlying the effects of H(2)S are unclear in the anesthetized rat. The objective of the present study was to investigate the effect of H(2)S on the electrocardiogram and examine the relationship between H(2)S-induced changes in heart rate (HR), mean arterial pressure (MAP), and respiratory function. Intravenous administration of the H(2)S donor Na(2)S in the anesthetized Sprague-Dawley rat decreased MAP and HR and produced changes in respiratory function. The administration of Na(2)S 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 Na(2)S-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, Na(2)S-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 Na(2)S could be dissociated and were independent of changes in respiratory function, ATP-sensitive K(+) channels, methylene blue-sensitive mechanism involving L-type voltage-sensitive Ca(2+) 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 H(2)S is a gasotransmitter capable of producing a decrease in mean arterial pressure and heart rate. The hypotensive and bradycardic effects of H(2)S can be dissociated, as shown with cardiac pacing experiments. Responses were not blocked by diltiazem, ivabradine, methylene blue, or glybenclamide.