Affinity of isoxsuprine for adrenoreceptors in equine digital artery and implications for vasodilatory action.
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.
Belloli
C
C
Institute of Veterinary Pharmacology and Toxicology, University of Milan, Italy.
Carcano
R
R
Arioli
F
F
Beretta
C
C
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
D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D007556:Isoxsuprine