Inhibition of adenosine-induced coronary vasodilation by block of large- conductance Ca2+-activated K+ channels

F. Cabell, D. S. Weiss, J. M. Price

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Abstract

The aim of the present study was to investigate the contribution of large- conductance calcium-activated potassium (large-conductance K(Ca)) channels to adenosine (Ado)- and nitroprusside-mediated relaxation in small coronary arteries. Canine subepicardial arteries (170 ± 23 μm at 120 mmHg) were studied as in vitro pressurized vessels. Pressure-diameter experiments showed myogenic tone over a physiological range of pressures. Tone was increased with the thromboxane A2 analogue 9,11-dideoxy-11α,9α-epoxy- methanoprostaglandin F(2α) (U-46619). Tetraethylammonium (TEA+; 1 mM) significantly inhibited Ado-induced [and by implication, adenosine 3',5'- cyclic monophosphate (cAMP)-induced] relaxations at Ado concentrations ranging from 0.1 to 10 μM with maximal inhibition (61 ± 8%) at 1 μM Ado. The large-conductance K(Ca)-channel blocker iberiotoxin (IbTX; 0.01-0.1 μM) inhibited Ado-mediated relaxation in a concentration-dependent manner. Inhibition by IbTX increased with increasing vessel pressure (i.e., 45 ± 12% at 40 mmHg and 83 ± 20% at 120 mmHg). TEA+ had a minimal effect (8 ± 3%) on relaxation induced by nitroprusside. Similar results were found with acetylcholine and bradykinin. These results suggest that (in dog coronary arteries with diameter < 200 μm) large-conductance K(Ca)-channel modulation may play a major role in cAMP-mediated relaxation but is not significant in guanosine 3',5'-cyclic monophosphate-mediated relaxation.

Original languageEnglish (US)
Pages (from-to)H1455-H1460
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume267
Issue number4 36-4
StatePublished - Nov 9 1994

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Keywords

  • adenosine 3',5'-cyclic monophosphate
  • calcium-activated potassium channels
  • guanosine 3',5'-cyclic monophosphate
  • myogenic tone
  • resistance vessels
  • vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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