Beta 1 and beta 2 adrenoceptors are involved in mediating vasodilation in the human coronary artery.
We have characterized beta-adrenoceptors in the human coronary artery and investigated the mechanism underlying vasodilating activity of dilevalol, a non-selective beta-blocking agent with beta 2 agonist properties. Specific [125I]-pindolol binding was saturable, reversible and of high affinity (Kd = 91 +/- 7 pM; Bmax = 10 +/- 3 fmol/mg protein). Competition curves of [125I]-pindolol in the presence of ICI 118,551, a selective beta 2 antagonist, or CGP 20712A, a selective beta 1 antagonist, were best explained by a two-site binding model (48 +/- 5% beta 1 and 52 +/- 4% beta 2 receptors). In isolated coronary strips, isoproterenol induced a dose-dependent vasorelaxant effect which was blocked by either ICI 118,551 (100 nM) or CGP 20712A (100 nM). Dilevalol produced about 30-40% of vasodilating activity starting at a concentration of 100 nM. The response was antagonized selectively by ICI 118,551 suggesting that dilevalol produces vasodilation through the stimulation of beta 2 receptors. These findings show that in the human coronary artery both beta 1 and beta 2 receptor subtypes are present and mediate vasodilation. This suggests that the human coronary artery could be used for the evaluation of the vasodilating component of new beta-adrenoceptor blocking agents.
Research Laboratories, Schering-Plough S.p.A., Milan, Italy.
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Monopoli
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Conti
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Forlani
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Ongini
D000328:Adult; D001667:Binding, Competitive; D003331:Coronary Vessels / Q000502:physiology / Q000648:ultrastructure*; D015237:Dinoprost / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D007741:Labetalol / Q000494:pharmacology; D008297:Male; D010869:Pindolol / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D015237:Dinoprost; D010869:Pindolol; D007545:Isoproterenol; D007741:Labetalol