Work from our laboratory has published new insights into how the gasotransmitter hydrogen sulfide (H2S) regulates ischemic vascular remodeling and how its metabolites are affected during clinical cardiovascular disease. While the field of H2S biomedical research has grown, many key gaps remain in understanding how sulfide metabolites are formed in the vasculature and their ultimate fate. In brief, our team revealed that H2S bioavailability quickly increases during chronic vascular/tissue ischemia contributing to a compensatory increase in nitric oxide levels. We further found that hydrogen sulfide dependent nitric oxide (NO) enhancement occurs in a dual fashion through its generation by nitric oxide synthases and by stimulation of nitrite reduction back to NO in a xanthine oxidase dependent manner.