ACUTE EFFECTS OF THYROID-HORMONE ON VASCULAR SMOOTH-MUSCLE

The enhanced cardiovascular hemodynamics associated with triiodo-L-thy ronine (T-3) treatment is in part mediated by a decrease in systemic v ascular resistance. To determine the molecular mechanisms for the vaso active properties of T-3, We studied primary cultures of aortic endoth elial and vascular smooth muscle (VSM) cells. Active tension developme nt by the VSM cells was measured by deformation lines within a siloxan e matrix on which the cells were grown. Exposure to T-3 (10(-10) M) re sulted in cellular relaxation within 10 min. Hormone binding studies t o purified VSM cell plasma membranes identified two binding sites spec ific for T-3 with K-d of 1 x 10(-11) and 6.1 x 10(-8) M. L-Thyroxine a nd reverse T-3 did not compete for the L-T-3 binding sites. To determi ne an intracellular signaling pathway of T-3 action, cAMP and cGMP con tent were measured in VSM cell cultures treated with T-3. No quantitat ive changes were observed in a time frame known to cause VSM cell rela xation. The level of myosin light chain phosphorylation is a major det erminant of smooth muscle contraction. Thus, treatment of VSM cells wi th isoproterenol, a vasodilator, caused a significant decrease in radi olabeled phosphate incorporation into the myosin light chains, whereas T-3 had no effect on phosphorylation of these proteins. Primary cultu res of vascular endothelial cells exposed to T-3 showed no nitric oxid e production as measured by cellular cGMP content and nitrite release, suggesting that T-3 acted directly on the VSM cell to cause vascular relaxation.