Changes in vascular reactivity induced by acute hyperthyroidism in isolated rat aortae

Hyperthyroidism was induced by subcutaneous injections Of L-thyroxine (T-4) (500 mg/kg/day) for 3 days in order to study whether adrenergic and muscar inic receptor-mediated vascular responses alter at an early stage of the di sease. T-4 treatment was sufficient to induce a significant degree of thyro id weight loss, tachycardia, cardiac hypertrophy, and an elevation in serum T-4 levels. The tension of aortic ring preparations isolated from rats was measured isometrically to investigate the influence of acute hyperthyroidi sm. The contractions induced by norepinephrine (NE) were significantly supp ressed in aortic rings from rats treated with T-4 compared with control rat s. N-G-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide synthase (N OS), significantly enhanced NE-induced contraction in aortic rings from bot h control and T-4-treated rats, and the enhancement was greater in rats tre ated with T-4 than control rats. The relaxations induced by either acetylch oline (ACh) or sodium nitroprusside (SNP) were also significantly enhanced by T-4 treatment. L-NOARG abolished the relaxation induced by ACh in aortic rings from both control and T-4-treated rats. L-NOARG shifted SNP-induced relaxation curves of aortic rings from those of control rats to the left, b ut not with rats treated with T-4. T-4 treatment showed no influence on the amount of endothelial NOS (eNOS) protein. These results suggest that vascu lar responses alter at an early stage of hyperthyroidism and that it may be due to a modification in the NO system which is independent from the amoun t of eNOS protein. (C) 2001 Elsevier Science Inc. All rights reserved.