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 x 10(-11) and 6.1 x 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.