Adenosine contributes to hypoxia-induced vasodilation through ATP-sensitive K+ channel activation.
the relative contribution of adenosine and ATP-sensitive potassium (KATP) channels in hypoxia-induced vasodilation was studied in isolated, saline-perfused rabbit hearts under constant flow conditions. Adenosine infusion induced a dose-dependent reduction in coronary perfusion pressure. Inhibition of KATP-channels with glibenclamide (0.3 microM) significantly reduced the dilator response to adenosine (-26 +/- 6 ys. -6 +/- 2% at 1 microM), whereas those of 1 microM acetylcholine or 10 microM papaverine were unaffected. The dilator responses to the A1-receptor selective agonist, N6-cyclopentyladenosine (CPA), and the mixed A1- and A2-receptor agonist, 5'-(N-ethylcarboxamido) adenosine (NECA), were comparable to that of adenosine. Treatment with glibenclamide reduced partially but significantly the NECA-induced vasodilation (-28 +/- 4 vs. -17 +/- 4%) and changed the CPA dilator response to a significant vasoconstriction. Both the nonselective adenosine-receptor antagonist, 8-phenyltheophylline (10 microM), and glibenclamide blocked the dilator response to adenosine and significantly reduced the hypoxia-induced vasodilation to the same extent. In conclusion, we suggest that the activation of KATP channels plays a major role in hypoxia-induced vasodilation. A major part of this activation results from the action of adenosine on receptors closely related to the A1 type.
Nakhostine
N
N
Research Center, Hôpital du Sacré-Coeur de Montréal, Quebec, Canada.
Lamontagne
D
D
D000241:Adenosine / Q000494:pharmacology* / Q000502:physiology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D014664:Vasodilation
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D000241:Adenosine