title: Contribution of hydrogen sulfide to the control of coronary blood flow.
abstract: 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.
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Eli D
authors.initials: ED
authors.lastname: Casalini
authors.forename: Adam G
authors.initials: AG
authors.lastname: Goodwill
authors.forename: Meredith K
authors.initials: MK
authors.lastname: Owen
authors.forename: Steven P
authors.initials: SP
authors.lastname: Moberly
authors.forename: Zachary C
authors.initials: ZC
authors.lastname: Berwick
authors.forename: Johnathan D
authors.initials: JD
authors.lastname: Tune
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D005260:Female; D064426:Gasotransmitters / Q000494:pharmacology*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism
chemical_list: D064426:Gasotransmitters; D006862:Hydrogen Sulfide
keywords: K channels; coronary circulation; reactive hyperemia
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