The direct vasomotor effect of thyroid hormones on rat skeletal muscle resistance arteries

The present study examines the hypothesis that the hormones have direct vasodilatory effects and attempts to determine whether the eff;cts are endothelium-dependent. Rat skeletal muscle resistance arteries of approximately 100 mu m were dissected, and vessel diameter changes were monitored using a videodetection system. After equilibration at 37 degrees C, each vessel was preconstricted with the thromboxane analog U46619 1 mu M, and the percentage of dilation was measured after exposure to increasing concentrations of triiodothyronine (T3) or levothyroxine (T4) (10(-10) to 10(-7) M). Dilation in response to T3 was also measured after endothelial denudation and pretreatment with the nitric oxide (NO) synthase inhibitor N-G-nitro-L-arginine (L-NNA) 10 mu M, the cyclooxygenase inhibitor indomethacin 10 mu M, the adenosine triphosphate-sensitive K+ channel blocker glibenclamide 1 mu M, or the beta-adrenergic antagonist propranolol 1 mu M. Both T3 and T4 demonstrated concentration-dependent dilation of the U46619-preconstricted vessels (P < 0.001 each), with T3 having a greater effect than T4 (P < 0.05)(36%+/-9% [mean+/-SD] dilation at 10(-7) M T3 vs 24%+/-6% dilation at 10(-7) M T4). In comparison, isoproterenol 10(-7) M produced 56%+/-6% dilation. T3-mediated vasodilation was attenuated but not abolished by endothelial denudation (18%+/-3% dilation at 10(-7) M T3) (P < 0.01), L-NNA (15%+/-7% dilation at 10(-7) M T3) (P < 0.01), indomethacin (20%+/-9% dilation at 10(-7) M T3) (P < 0.05), and glibenclamide (22%+/-7% dilation at 10(-7) M T3) (P < 0.01), but it was not affected by propranolol (37%+/-20% dilation at 10(-7) M T3) (P = 0.99). We conclude that thyroid hormones possess direct vasodilatory effects with both endothelium-independent and endothelium-independent components. Implications: Thyroid hormones may have modest direct vasodilatory effects. This may partially account for the cardiovascular actions of the hormones in hyperthyroidism or when administered pharmacologically in cardiac surgery.