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 system. Hyperthyroidism was induced by feeding rats for 28 days with 5 mg/kg L-thyroxine (T4)-containing rat chow. This treatment produced a stable hyperthyroid state, as indicated by several biochemical/metabolic and haemodynamic parameters. Preparations of small mesenteric arteries were mounted in an isometric wire myograph. Subsequently, concentration-effect curves were determined for isoproterenol, noradrenaline and salbutamol as well as for forskolin, dibutyryl-cAMP and theophylline. We 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 beta 2- and beta 1-adrenoceptor antagonist, respectively). Apparent pA2-values were calculated to determine which beta-adrenoceptor subtype causes vasodilation. These experiments indicate that beta-adrenoceptor-mediated vasodilation involves both beta 1- and beta 2-adrenoceptors in mesenteric resistance vessels of both hyperthyroid and control rats. In our experiments hyperthyroidism has a sensitizing influence on vascular responses induced by the beta-adrenoceptor agonist isoproterenol and the selective beta 2-adrenoceptor agonist salbutamol. Sensitization to isoproterenol was abolished in the presence of ICI 118,551, whereas it was emphasized in the presence of CGP 20712A. Although this was not fully supported by the results obtained with noradrenaline, these results indicate that the sensitization to beta-adrenoceptor agonists is probably limited to the beta 2-adrenoceptor/G-protein complex and not associated with alterations of the corresponding second messenger system.
Zwaveling
J
J
Department of Pharmacotherapy, University of Amsterdam, Netherlands.
Winkler Prins
E A
EA
Pfaffendorf
M
M
van Zwieten
P A
PA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006980:Hyperthyroidism / Q000139:chemically induced / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000503:physiopathology; D008729:Methoxamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D013974:Thyroxine; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D011412:Propanolamines; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D005576:Colforsin; C026777:ICI 118551; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C049763:CGP 20712A; D008729:Methoxamine; D007545:Isoproterenol; D013974:Thyroxine; D000420:Albuterol