Acute Effects of Thyroid Hormone on Vascular Smooth Muscle

The enhanced cardiovascular hemodynamics associated with triiodo- L -thyronine (T 3 ) treatment is in part mediated by a decrease in systemic vascular resistance. To determine the molecular mechanisms for the vasoactive properties of T 3 , we studied primary cultures of aortic endothelial and vascular smooth muscle (VSM) cells. Active tension development by the VSM cells was measured by deformation lines within a siloxane matrix on which the cells were grown. Exposure to T 3 (10 -10 M) resulted in cellular relaxation within 10 min. Hormone binding studies to purified VSM cell plasma membranes identified two binding sites specific for T 3 with K d of 1 × 10 -11 and 6.1 × 10 -8 M. L -Thyroxine and reverse T 3 did not compete for the L -T 3 binding sites. To determine an intracellular signaling pathway of T 3 action, cAMP and cGMP content were measured in VSM cell cultures treated with T 3 . No quantitative changes were observed in a time frame known to cause VSM cell relaxation. The level of myosin light chain phosphorylation is a major determinant of smooth muscle contraction. Thus, treatment of VSM cells with isoproterenol, a vasodilator, caused a significant decrease in radiolabeled phosphate incorporation into the myosin light chains, whereas T 3 had no effect on phosphorylation of these proteins. Primary cultures of vascular endothelial cells exposed to T 3 showed no nitric oxide production as measured by cellular cGMP content and nitrite release, suggesting that T 3 acted directly on the VSM cell to cause vascular relaxation.