Role of Hydrogen Sulfide in the Regulation of Coronary Blood Flow

Abstract

This study examined mechanisms by which hydrogen sulfide (H2S) regulates coronary blood flow. Experiments were conducted in open‐chest anesthetized dogs while coronary perfusion pressure was held constant at 100 mmHg with a servo‐controlled roller pump. We found that intracoronary (ic) administration of H2S (0.1–3 mM) increased coronary flow from 0.49 ± 0.08 to 2.65 ± 0.13 ml/min/g (P < 0.001). This increase in flow was unaffected by inhibition of Kv channels with 4‐aminopyridine (0.3 mM, ic) but was significantly attenuated (57%) by the KATP channel antagonist glibenclamide (3mg/kg, iv; P < 0.001). Coronary responses to H2S were not diminished by inhibition of NO synthesis with L‐NAME (150 ug/min, ic). Immunohistochemistry revealed expression of the H2S producing enzyme cystathionine gamma‐lyase (CSE) in myocardium. Inhibition of CSE with β‐cyano‐L‐alanine (BCA) (10 μM, ic) had no effect on baseline coronary flow or flow responses to a brief coronary artery occlusion; repayment/debt ratio for control and BCA responses were 465 ± 42% vs. 453 ± 27% respectively. These findings indicate that H2S produces marked, endothelium‐independent vasodilation in the coronary circulation via activation of smooth muscle KATP channels. Despite these effects, our data suggest that endogenous production of H2S is not required for regulation of baseline coronary flow or vasodilation in response to myocardial ischemia. (Support: HL092245)