title: Affinity of isoxsuprine for adrenoreceptors in equine digital artery and implications for vasodilatory action.
abstract: We used isolated equine digital arteries to study the vasodilatory mechanism of isoxsuprine, and fowl caecum preparations to investigate the affinity of the drug for beta-adrenoceptors. Isoxsuprine is a potent vasodilator of arterial smooth muscle that has been precontracted by an alpha-adrenoceptor agonist such as noradrenaline (log EC50 = -6.33 [-5.98; -6.68]). The present study indicates that its effect is due to alpha-adrenoceptor blockade since: (1) after a long lasting exposure to cumulative doses of isoxsuprine the vasoconstricting action of noradrenaline cannot be restored; (2) isoxsuprine does not promote relaxation on preparations precontracted by PGF2alpha; (3) isoxsuprine shifts the dose-response curve of noradrenaline to the right; and (4) its affinity (pK(B) = 6.90 [6.60; 7.20]) in this experiment is comparable to that in noradrenaline-precontracted preparations and is 14 times lower than that of the selective alpha1-adrenergic antagonist prazosin [pK(B) = 8.04 (7.40; 8.68]). The affinity of isoxsuprine for beta-adrenoceptors was 100 times lower than that of isoprenaline when tested on fowl caecum. This preparation has a large beta-adrenoceptor and negligible alpha-adrenoceptor population concerned with the control of smooth muscle motility. Our data suggest that the alpha-mediated effect of isoxsuprine on horse arterial smooth muscle is due to higher affinity of the drug for alpha- than beta-adrenoceptors rather than low concentration or functionality of beta-sites at this site. According to these data, pure beta2-agonists seem to be more profitable tools to determine vasodilation of the arterial bed in horses legs.
authors.affiliation: Institute of Veterinary Pharmacology and Toxicology, University of Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Belloli
authors.forename: R
authors.initials: R
authors.lastname: Carcano
authors.forename: F
authors.initials: F
authors.lastname: Arioli
authors.forename: C
authors.initials: C
authors.lastname: Beretta
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D001158:Arteries / Q000378:metabolism*; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D005552:Forelimb / Q000098:blood supply*; D006736:Horses / Q000378:metabolism*; D007545:Isoproterenol / Q000378:metabolism; D007556:Isoxsuprine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D014664:Vasodilation
chemical_list: D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D007556:Isoxsuprine