Effect of hypothyroidism on beta-adrenoceptor-mediated relaxation in the rat thoracic aortae. A time-dependent study.
We investigated the time dependency of hypothyroid-induced changes in beta-adrenoceptor-mediated relaxation of vascular smooth muscle. Methimazole (0.03%) was administered to male Wistar-Imamichi rats for 3 days, 1, 2 or 6 weeks. This treatment led to significant increases in thyroid weight while inhibiting growth rate. Tension in isolated rings of thoracic aortae from control and hypothyroid rats was measured isometrically. Responses of aortic rings to cumulative doses of acetylcholine (ACh) and sodium nitroprusside (SNP) were not significantly different between control and hypothyroid groups. After 3 days and 1 week of treatment, isoprenaline (ISO)-induced relaxation was unchanged, but after 2 and 6 weeks, a marked increase was observed as compared to controls. Removal of the endothelium and pretreatment with NG-nitro-L-arginine (L-NOARG) inhibited the ISO-induced relaxation in both groups; but whereas this degree of inhibition was the same for both groups after 3 days and 1 week, it was significantly less pronounced in hypothyroid rats after 2 and 6 weeks as compared to their controls. These results suggest that hypothyroidism has a time-dependent influence on beta-adrenoceptor-mediated relaxation in the rat thoracic aortae and that the enhancement after 2 and 6 weeks of methimazole treatment may be due to a hypothyroid-induced alteration in arterial smooth muscle function.
Ampong
Beryl
B
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 193-0392, Japan.
Honda
Hideo
H
Kogo
Hiroshi
H
D000109:Acetylcholine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology; D007037:Hypothyroidism / Q000139:chemically induced / Q000503:physiopathology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008713:Methimazole / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D013956:Antithyroid Agents; D011943:Receptors, Adrenergic, beta; D009599:Nitroprusside; D008713:Methimazole; D007545:Isoproterenol; D000109:Acetylcholine