Endogenous nitric oxide masks α2-adrenergic coronary vasoconstriction during exercise in the ischemic heart

Yutaka Ishibashi, Dirk J. Duncker, Robert J. Bache

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35 Scopus citations

Abstract

Previously, we observed that α1- but not α2-adrenergic vasoconstriction restricted blood flow distal to a coronary artery stenosis that resulted in myocardial hypoperfusion during exercise. This study was performed to test the hypothesis that vascular smooth muscle α2-adrenergic vasoconstriction during exercise does exert a flow-limiting effect distal to a coronary artery stenosis but that this action is counterbalanced by simultaneous endothelial α2-adrenergic stimulation of NO production. Eight dogs instrumented with a Doppler velocity probe, hydraulic occluder, and indwelling microcatheter in the left anterior descending coronary artery (LAD) were studied during treadmill exercise in the presence of a coronary artery stenosis before and during infusion of the α-adrenergic receptor antagonist idazoxan (1.0 μg · kg-1 · min-1 IC) before and after NO synthase blockade with N(G)-monomethyl-L-arginine (LNNA, 1.5 mg/kg IC). Coronary pressure distal to the stenosis was maintained constant during the control period and after administration of idazoxan before and after LNNA. Neither idazoxan nor LNNA altered any of the systemic hemodynamic variables either at rest or during exercise. During exercise in the absence of a stenosis, idazoxan and LNNA had no effect on coronary blood flow. In the presence of a stenosis that decreased distal coronary pressure to 52±3 mm Hg, mean myocardial blood flow measured with microspheres was 0.87±0.17 mL · min-1 · g-1 in the LAD-dependent region and 2.52±0.30 mL · min-1 · g-1 in the posterior control region, respectively. With no change in distal coronary pressure, idazoxan had no effect on mean myocardial blood flow in the LAD region (0.86±0.17 mL · min-1 · g-1), but LNNA decreased mean myocardial blood flow to 0.49±0.09 (P<.01). However, when idazoxan was infused during exercise in the presence of a coronary artery stenosis after LNNA administration, idazoxan increased mean myocardial blood flow to 0.62±0.13 mL · min-1 · g-1 (P<.01). These data demonstrate that α2-adrenergic stimulation of endothelial NO production, which occurs during exercise in the presence of a flow-limiting coronary artery stenosis, acts to counterbalance vascular smooth muscle α2-adrenergic vasoconstriction.

Original languageEnglish (US)
Pages (from-to)196-207
Number of pages12
JournalCirculation research
Volume80
Issue number2
DOIs
StatePublished - 1997

Keywords

  • N(G)-nitro-L- arginine
  • adrenergic vasoconstriction
  • coronary vasodilation
  • endothelium
  • idazoxan

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