Altered mechanism of adenosine-induced coronary arteriolar dilation in early-stage metabolic syndrome

Shawn B. Bender, Johnathan D. Tune, Lena Borbouse, Xin Long, Michael Sturek, M. Harold Laughlin

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Onset of the combined metabolic syndrome (MetS) is a complex progressive process involving numerous cardiovascular risk factors. Although patients with established MetS exhibit reduced coronary flow reserve and individual components of the MetS reduce microvascular vasodilation, little is known concerning the impact of early-stage MetS on the mechanisms of coronary flow control. Therefore, we tested the hypothesis that coronary arteriolar dilation to adenosine is attenuated in early-stage MetS by reduced A2 receptor function and diminished K+ channel involvement. Pigs were fed control or high-fat/cholesterol diet for 9 weeks to induce early-stage MetS. Coronary atheroma was determined in vivo with intravascular ultrasound. In vivo coronary dilation was determined by intracoronary adenosine infusion. Further, apical coronary arterioles were isolated, cannulated and pressurized to 60 cmH 2O for in vitro pharmacologic assessment of adenosine dilation. Coronary atheroma was not different between groups, indicating early-stage MetS. Coronary arteriolar dilation to adenosine (in vivo) and 2-chloroadenosine (2-CAD; in vitro) was similar between groups. In control arterioles, 2-CAD-mediated dilation was reduced only by selective A2A receptor inhibition, whereas only dual A2A/2B inhibition reduced this response in MetS arterioles. Arteriolar A2B, but not A2A, receptor protein expression was reduced by MetS. Blockade of voltage-dependent K + (Kv) channels reduced arteriolar sensitivity to 2-CAD in both groups, whereas ATP-sensitive K+ (KATP) channel inhibition reduced sensitivity only in control arterioles. Our data indicate that the mechanisms mediating coronary arteriolar dilation to adenosine are altered in early-stage MetS prior to overt decrements in coronary vasodilator reserve.

Original languageEnglish (US)
Pages (from-to)683-692
Number of pages10
JournalExperimental Biology and Medicine
Volume234
Issue number6
DOIs
StatePublished - Jun 1 2009

Keywords

  • Adenosine receptor
  • Coronary blood flow
  • Diabetes
  • Obesity
  • Ossabaw miniature swine
  • Potassium channel

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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