Acute effects of thyroid hormone on vascular smooth muscle.
The enhanced cardiovascular hemodynamics associated with triiodo-L-thyronine (T3) treatment is in part mediated by a decrease in systemic vascular resistance. To determine the molecular mechanisms for the vasoactive properties of T3, 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 T3 (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 T3 with Kd of 1 x 10(-11) and 6.1 x 10(-8) M. L-Thyroxine and reverse T3 did not compete for the L-T3 binding sites. To determine an intracellular signaling pathway of T3 action, cAMP and cGMP content were measured in VSM cell cultures treated with T3. 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 T3 had no effect on phosphorylation of these proteins. Primary cultures of vascular endothelial cells exposed to T3 showed no nitric oxide production as measured by cellular cGMP content and nitrite release, suggesting that T3 acted directly on the VSM cell to cause vascular relaxation.
Ojamaa
K
K
Department of Medicine, North Shore University Hospital/NYU School of Medicine, Manhasset 11030, USA.
Klemperer
J D
JD
Klein
I
I
D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D018994:Myosin Light Chains / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction; D014284:Triiodothyronine / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D018994:Myosin Light Chains; D014284:Triiodothyronine; D009569:Nitric Oxide; D000242:Cyclic AMP; D006152:Cyclic GMP