Contribution of Hydrogen Sulfide to the Control of Coronary Blood Flow. (February 2014)

• Record Type: Journal Article
• Authors: Casalini, Eli D.; Goodwill, Adam G.; Owen, Meredith K.; Moberly, Steven P.; Berwick, Zachary C.; Tune, Johnathan D.
• Is Part Of: Microcirculation. Volume 21:Number 2(2014:Feb.)
• Page Start: 104
• Page End: 111
• Publication Date: 2014-02
• Subjects: Biological transport -- Periodicals; Microcirculation -- Physiology -- Periodicals; 612.135
• DOI: 10.1111/micc.12083
• Languages: English
• ISSNs: 1073-9688

Abstract

<abstract abstract-type="main" id="micc12083-abs-0001"> <title>Abstract</title> <sec id="micc12083-sec-0001" sec-type="section"> <title>Objective</title> <p>This study examined the mechanisms by which H<sub>2</sub>S modulates coronary microvascular resistance and myocardial perfusion at rest and in response to cardiac ischemia.</p> </sec> <sec id="micc12083-sec-0002" sec-type="section"> <title>Methods</title> <p>Experiments were conducted in isolated coronary arteries and in open‐chest anesthetized dogs.</p> </sec> <sec id="micc12083-sec-0003" sec-type="section"> <title>Results</title> <p>We found that the H<sub>2</sub>S substrate <sc>l</sc>‐cysteine (1–10 mM) did not alter coronary tone of isolated arteries <italic>in vitro</italic> or coronary blood flow <italic>in vivo</italic>. In contrast, intracoronary (ic) H<sub>2</sub>S (0.1–3 mM) increased coronary flow from 0.49 ± 0.08 to 2.65 ± 0.13 mL/min/g (<italic>p < </italic>0.001). This increase in flow was unaffected by inhibition of K<sub>v</sub> channels with 4‐aminopyridine (<italic>p </italic>= 0.127) but was attenuated (0.23 ± 0.02–1.13 ± 0.13 mL/min/g) by the K<sub>ATP</sub> channel antagonist glibenclamide (<italic>p < </italic>0.001). Inhibition of NO synthesis (<sc>l</sc>‐NAME) did not attenuate coronary responses to H<sub>2</sub>S. Immunohistochemistry revealed expression of CSE, an endogenous H<sub>2</sub>S enzyme, in myocardium. Inhibition of CSE with β‐cyano‐<sc>l</sc>‐alanine (10 μM) had no effect on baseline coronary flow or responses to a 15‐second coronary occlusion (<italic>p </italic>= 0.82).</p> </sec> <sec id="micc12083-sec-0004" sec-type="section"> <title>Conclusions</title> <p>These findings demonstrate that exogenous H<sub>2</sub>S induces potent, endothelial‐independent dilation of the coronary microcirculation predominantly through the activation of K<sub>ATP</sub> channels, however, our data do not support a functional role for endogenous H<sub>2</sub>S in the regulation of coronary microvascular resistance.</p> </sec> </abstract>