The present study examines the hypothesis that the hormones have direct vasodilatory effects and attempts to determine whether the effects are endothelium-dependent. Rat skeletal muscle resistance arteries of approximately 100 microns 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 microM, 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 NG-nitro-L-arginine (L-NNA) 10 microM, the cyclooxygenase inhibitor indomethacin 10 microM, the adenosine triphosphate-sensitive K+ channel blocker glibenclamide 1 microM, or the beta-adrenergic antagonist propranolol 1 microM. 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-dependent 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.