Inhibition of Cystathionine Beta‐Synthase (CBS) Decreases Acetylcholine Mediated Relaxation in Murine Aorta and Mesenteric Arteries

Hydrogen sulfide (H 2 S) is a novel gas involved in the regulation of blood pressure and vascular function, exhibiting a potent vasorelaxant effect alongside nitric oxide (NO) and carbon monoxide (CO). H 2 S is generated endogenously from cysteine by three enzymes: cystathionine beta‐synthase (CBS), cystathionine gamma‐lyase (CSE) and 3‐mercaptopyruvate sulfurtransferase (3‐MST). Although predominant interest has been given to the role of CSE in the cardiovascular system, the role of CBS has been poorly investigated. We hypothesize that H2S generation by CBS plays an important role in vascular function, and the inhibition of this enzyme leads to decreased relaxation. In aorta, Inhibition of CBS using amino oxyacetic acid (AOAA, 3 mM) leads to a significant decrease in sensitivity (EC 50 ) to acetylcholine (ACh); however, it did not affect the maximal relaxation. In mesenteric artery, inhibition of CBS leads to a significant decrease in sensitivity and maximal relaxation response to Ach. Inhibition of CBS did not affect sodium nitroprusside (SNP) mediated relaxation in either aorta or mesenteric arteries. These data suggest that CBS plays an important role in the regulation of vascular tone and that CBS inhibition leads to decreased endothelium dependant‐relaxation.