Mechanisms of Hydrogen Sulfide‐induced Vasomodulatory Responses: Comparisons Between Rat Pulmonary Arteries and Thoracic Aorta.

Abstract

Hydrogen Sulfide (H2S), a third endogenously produced gaseous mediator, was reported to produce a dual vascular response in rat isolated thoracic aorta (TA). To determine the cellular mechanisms as well as tissue specificity, we compared H2S effects on rat pulmonary arteries (PA) and TA in the presence and absence of endothelium (EC) and L-NAME. In all EC-intact and phenylephrine-precontracted PA and TA, addition of sodium hydrosulfide (H2S donor, 3 to 30 μM) resulted in a dose-dependent contraction (Emax= 8±1% and 19±4%, respectively), whereas higher doses (0.1 to 1.0 mM) produced a dose-dependent relaxation (Emax= −88±2% and −40±5%, respectively). EC disruption, L-NAME pretreatment or 40mM KCl precontraction completely abolished the H2S contraction, while the observed relaxation in PA, but not TA, was reduced to half (−50±4%, −60±3% and −49±3%, respectively). The latter relaxation response in both PA and TA was equally inhibited by glybenclamide and higher KCl (70 mM), but was insensitive to ODQ. Consistent with the early report, the present finding of contraction with low H2S doses was probably related to its chemical inactivation of the spontaneously produced NO. However, H2S was less effective as hemoglobin inactivation of NO or L-NAME inhibition of spontaneous NO production, which consistently produced a 44±5% and 77±11% contraction in PA and TA under identical condition. While the higher dose H2S-induced relaxation in TA appears to be EC/NO-independent, the PA response involved a dual mechanism. Taken together, these findings suggest that H2S vasomodulatory responses and its interaction with NO are complex and there also exist a marked tissue difference in their responses. (Supported by NIH NCCAM RO1 AT-001235)