Comparison of muscarinic receptor- and beta-adrenoceptor-mediated vasorelaxation between euthyroid and acute hyperthyroid rats.
Hyperthyroidism was induced by subcutaneous injections of L-thyroxine (T4) (0.5 mg/kg/day) for 3 days in order to investigate the effects of acute hyperthyroidism on the vasorelaxing responses to isoprenaline and acetylcholine in isolated rat aortae. In the aortae, there was no significant difference in isoprenaline-induced relaxation between hyperthyroid and control rats, however acetylcholine-induced relaxation was significantly greater in hyperthyroid rats than in control rats. N(G)-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide (NO) synthase, reduced isoprenaline- and acetylcholine-induced relaxations in both hyperthyroid and control rats and in the presence of L-NOARG no significant difference in the acetylcholine-induced relaxation was seen between the two groups of rats. Indomethacin, a cyclo-oxygenase inhibitor, had no significant influence on both isoprenaline- and acetylcholine-induced relaxations in both control and hyperthyroid rats. 17-Octadecynoic acid (17-ODYA), a cytochrome P-450 mono-oxygenase inhibitor, reduced the both isoprenaline- and acetylcholine-induced relaxation in both hyperthyroid and control rats, and acetylcholine-induced relaxation was still greater in hyperthyroid rats than in control rats. These results indicate that an acute hyperthyroidism significantly enhances muscarinic receptor- but not adrenoceptor-mediated relaxations of the aortae and L-NOARG abolished an enhancement by acute hyperthyroidism of muscarinic receptor-mediated relaxation, suggesting that the effects may be due to an alteration in muscarinic receptor-mediated NO systems of the aortae at early stage of hyperthyroidism.
Honda
H
H
Department of Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 193-0392, Japan. hhonda@ps.toyaku.ac.jp
Iwata
T
T
Matsuda
H
H
Moroe
H
H
Kumasaka
K
K
Kondo
M
M
D000109:Acetylcholine / Q000627:therapeutic use*; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006980:Hyperthyroidism / Q000188:drug therapy* / Q000503:physiopathology; D007545:Isoproterenol / Q000627:therapeutic use*; D008297:Male; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D011950:Receptors, Cholinergic; D014665:Vasodilator Agents; D019335:Nitroarginine; C047008:17-octadecynoic acid; D007545:Isoproterenol; D000109:Acetylcholine