Cystathionine beta-synthase (CBS) inhibition decreased acetylcholine mediated relaxation in murine resistance arteries; a potential role for hydrogen sulfide in endothelium mediated relaxation

Hydrogen sulfide (H2S) is a novel gas involved in the regulation of blood pressure and vascular function. Recently, H2S was described as a potent vasorelaxant molecule alongside nitric oxide(NO) and carbon monoxide (CO). H2S is generated endogenously mainly by two enzymes: cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE). Although predominant interest has been given to the role of CSE in the cardiovascular system, the role of CBS has been poorly investigated. Using pharmacological as well as genetic tools, we are seeking to elucidate the role of CBS in the vasculature. We hypothesize that H2S generation by CBS is required for vascular function, and the inhibition of this enzyme leads to decreased vaso-relaxation. CBS deficiency (CBS+/-) leads to a significant decreased in Ach mediated relaxation in mesenteric artery rings (89.16±4.99%in CBS+/+vs62.94±4.57% in CBS+/-).Furthermore, incubation of isolated CBS+/+ mesenteric arteries with the CBS inhibitor, aminooxyacetic acid (AOAA, 3 mM) similarly resulted in a significant decrease in Ach mediated relaxation (45.62±12.10% AOAAvs89.16±4.99% control). These data suggest that CBS plays an important role in the regulation of contractile tone of resistance arteries.