Characterisation of beta-adrenoceptors in equine digital veins: implications of the modes of vasodilatory action of isoxsuprine.

Abstract: Isolated equine digital veins (EDVs) were used to study beta-adrenoceptor mediated vasodilation and to examine isoxsuprine's vasodilatory mechanism of action. When the blood vessel wall tension was raised with potassium chloride solution (KCl; 59 mmol/l), the order of vasodilator potency of beta-agonists was: isoprenaline > fenoterol > noradrenaline > dobutamine > isoxsuprine. The beta 2-selective adrenoceptor antagonist, ICI 118551 (1 nmol/l) caused a 6.74 and 6.65-fold parallel shift to the right in the dose response curves to fenoterol and noradrenaline respectively. Propranolol (10 nmol/l) inhibited the vasodilatory action of isoprenaline in a competitive manner (19.6 +/- 6.4-fold parallel shift to the right) but was much less effective as an inhibitor of isoxsuprine's vasodilatory action. Isoprenaline and fenoterol were just as effective as vasodilators when blood vessel wall tension was raised with KCl, the thromboxanemimetic U44069 (9, 11-dideoxy-9 alpha, 11 alpha-epoxymethano-prostaglandin F2 alpha; 30 nmol/l) or the alpha 1-adrenoceptor agonist, phenylephrine (0.3 mumol/l). In addition, fenoterol's relaxation of U44069-induced tone was competitively inhibited by the beta 2-selective adrenoceptor antagonist ICI 118551 (8.4 +/- 0.9-fold parallel shift to the right). By contrast, isoxsuprine was 81.9 times more potent as a vasorelaxant of phenylephrine-induced tone when compared with KCl-induced tone and proved completely ineffective as a vasodilator of U44069-induced tone. When dose response curves to alpha-adrenoceptor vasoconstrictor agonists were obtained in the presence of isoxsuprine (0.1 mumol/l), competitive antagonism occurred with methoxamine and noncompetitive antagonism with BHT-920. These data suggest EDVs possess beta 2-adrenoceptors mediating vasodilation. Isoxsuprine is an alpha 1-selective adrenoceptor antagonist but has very low potency and efficacy as a beta-adrenoceptor agonist in this functional bioassay. Indeed, much of the vasodilatory action of isoxsuprine may be due to a mechanism which does not involve beta-adrenoceptors.