THE INFLUENCE OF HYPERTHYROIDISM ON BETA-ADRENOCEPTOR-MEDIATED RELAXATION OF ISOLATED SMALL MESENTERIC-ARTERIES

We investigated the influence of hyperthyroidism on relaxant responses of small mesenteric resistance arteries to beta-adrenoceptor agonists and to compounds stimulating the corresponding second-messenger syste m. Hyperthyroidism was induced by feeding rats for 28 days with 5 mg/k g L-thyroxine (T4)-containing rat chow. This treatment produced a stab le hyperthyroid state, as indicated by several biochemical/metabolic a nd haemodynamic parameters. Preparations of small mesenteric arteries were mounted in an isometric wire myograph. Subsequently, concentratio n-effect curves were determined for isoproterenol, noradrenaline and s albutamol as well as for forskolin, dibutyryl-cAMP and theophylline. W e also determined concentration-effect curves to the beta-adrenoceptor agonists in the presence of ICI 118,551 and CGP 20712A (i.e., in the presence of a selective B-2- and B-1-adrenoceptor antagonist, respecti vely). Apparent pA(2)-values were calculated to determine beta-adrenoc eptor subtype causes vasodilation. experiments indicate that beta-adre noceptor-mediated vasodilation involves both beta(1)- and beta(2)-adre noceptors in mesenteric resistance vessels of both hyperthyroid and co ntrol rats. In our experiments hyperthyroidism has a sensitizing influ ence on vascular responses induced by the beta-adrenoceptor agonist is oproterenol and the selective beta(2)-adrenoceptor agonist salbutamol. Sensitization to isoproterenol was abolished in the presence of ICI 1 18,551, whereas it was emphasized in the presence of CGP 20712A. Altho ugh this was not fully supported by the results obtained with noradren aline, these results indicate that the sensitization to beta-adrenocep tor agonists is probably limited to the beta(2)-adrenoceptor/G-protein complex and not associated with alterations of the corresponding seco nd messenger system.