The role of α1- and α2-adrenergic receptors in mediation of coronary vasoconstriction in hypoperfused ischemic myocardium during exercise

D. D. Laxson, X. Z. Dai, D. C. Homans, R. J. Bache

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Abstract

This study was carried out to test the hypothesis that adrenergic coronary vasoconstriction limits blood flow to hypoperfused regions of myocardium during exercise. The vasoconstrictor influence of α-adrenergic receptor subtypes was assessed by use of selective adrenergic blocking agents. Dogs chronically instrumented with a circumflex coronary artery hydraulic occluder and an intra-arterial catheter underwent treadmill exercise in the presence of a coronary stenosis that decreased distal perfusion pressure to 40 mm Hg. Myocardial blood flow was measured with radioactive microspheres (15 μm) before and during selective α1- or α2-adrenergic receptor blockade produced by intracoronary infusion of prazosin (1 μg/kg/min x 10 min) or idazoxan (1 μg/kg/min x 10 min), respectively. Coronary perfusion pressure was held equal before and during receptor blockade with the hydraulic occluder. Compared with control exercise, subendocardial blood flow increased during α1-receptor blockade with prazosin from 0.60 ± 0.14 to 1.12 ± 0.17 ml/min/g p < 0.05), and mean transmural flow increased from 1.07 ± 0.19 to 1.60 ± 0.22 ml/min/g (p < 0.05). In contrast, subendocardial and mean transmural blood flow were not different from control during selective α2-adrenergic receptor blockade with idazoxan (0.48 ± 0.10 vs. 0.67 ± 0.14 ml/min/g, p = 0.33, and 0.82 ± 0.15 vs. 1.02 ± 0.20 ml/min/g, p = 0.45, respectively). These data indicate that even in the presence of a coronary stenosis that causes substantial myocardial underperfusion during exercise, residual coronary vasoconstrictor tone is present in ischemic myocardium, and this vasoconstriction is mediated predominantly by the α1-adrenergic receptor.

Original languageEnglish (US)
Pages (from-to)1688-1697
Number of pages10
JournalCirculation research
Volume65
Issue number6
DOIs
StatePublished - 1989

Keywords

  • coronary circulation
  • idazoxan
  • myocardial ischemia
  • prazosin
  • α-adrenergic receptors

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