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-receptor-mediated vasorelaxation in hypoxic
porcine coronary artery
Department of Anesthesiology, Niigata University School of Medicine, Niigata 951-8510, Japan
To investigate the
-adrenoceptor-mediated
responses in hypoxic coronary arteries, we studied the effect of
isoproterenol (Iso) on isolated porcine coronary arteries contracted
with endothelin-1 in media aerated with 0, 5, 7.5, and 95%
O2. The concentration-response curve of Iso was significantly shifted to the left by hypoxia (0 and
5% O2). In oxygenated and
hypoxic arteries, 3 × 10
8,
10
6, and
10
5 M Iso significantly
increased the contents of cAMP. However, there was no difference in the
increases of cAMP content induced by 3 × 10
8 M Iso between
oxygenated and hypoxic arteries. The content of cAMP induced by high
concentrations of Iso (10
6
and 10
5 M) was
significantly larger in hypoxic than in oxygenated arteries. Furthermore, the potentiation by hypoxia of the Iso-induced
vasorelaxation was inhibited by glibenclamide and depolarization by
KCl, but not by removal of endothelium and indomethacin. The
vasodilatory response to forskolin and dibutyryl cAMP was unaffected by
hypoxia. We conclude that activation of the ATP-sensitive
K+ channel may account for the
potentiation of the response to Iso in hypoxic coronary arteries.
isoproterenol; cyclic nucleotides; ATP-sensitive potassium channel; glibenclamide
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