Objective: This study examined the mechanisms by which H2 S modulates coronary microvascular resistance and myocardial perfusion at rest and in response to cardiac ischemia.
Methods: Experiments were conducted in isolated coronary arteries and in open-chest anesthetized dogs.
Results: We found that the H2 S substrate l-cysteine (1-10 mM) did not alter coronary tone of isolated arteries in vitro or coronary blood flow in vivo. In contrast, intracoronary (ic) H2 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 (p = 0.127) but was attenuated (0.23 ± 0.02-1.13 ± 0.13 mL/min/g) by the KATP channel antagonist glibenclamide (p < 0.001). Inhibition of NO synthesis (l-NAME) did not attenuate coronary responses to H2 S. Immunohistochemistry revealed expression of CSE, an endogenous H2 S enzyme, in myocardium. Inhibition of CSE with β-cyano-l-alanine (10 μM) had no effect on baseline coronary flow or responses to a 15-second coronary occlusion (p = 0.82).
Conclusions: These findings demonstrate that exogenous H2 S induces potent, endothelial-independent dilation of the coronary microcirculation predominantly through the activation of KATP channels, however, our data do not support a functional role for endogenous H2 S in the regulation of coronary microvascular resistance.
Keywords: K channels; coronary circulation; reactive hyperemia.
© 2013 John Wiley & Sons Ltd.