Role of Hydrogen Sulfide in the Regulation of Coronary Blood Flow

This study examined mechanisms by which hydrogen sulfide (H 2 S) 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 H 2 S (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 K ATP channel antagonist glibenclamide (3mg/kg, iv; P < 0.001). Coronary responses to H 2 S were not diminished by inhibition of NO synthesis with L‐NAME (150 ug/min, ic). Immunohistochemistry revealed expression of the H 2 S 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 H 2 S produces marked, endothelium‐independent vasodilation in the coronary circulation via activation of smooth muscle K ATP channels. Despite these effects, our data suggest that endogenous production of H 2 S is not required for regulation of baseline coronary flow or vasodilation in response to myocardial ischemia. (Support: HL092245)