THE DIRECT EFFECTS OF THYROID-HORMONES ON RAT MESENTERIC RESISTANCE ARTERIES

The direct relaxant effects of thyroid hormones on mesenteric resistan ce vessels were investigated using an isometric wire myograph. Both th e L- and the D-isomers of thyroxine (T-4) and triiodothyronine (T-3) w ere studied. In contrast with the long-term effects of thyroid hormone s, both T-4 enantiomers proved more potent in inducing vascular relaxa tion than the two T-3 enantiomers. The interaction between thyroid hor mones and calcium-induced contractions was studied. T-4 concentration dependently inhibited the Ca2+ induced contractions, showing noncompet itive interaction. Furthermore, we investigated whether the endotheliu m was involved in the relaxant effect to L-T-4. The T-4 induced relaxa tion proved impaired by prior incubation with the nitric oxide (NO) in hibitor N-omega-nitro-L-arginine methylester HCl (L-NAME, 0.1 mu M), i ndicating that T-4 is able to stimulate the production of endothelium- derived NO. L-T-4-induced relaxation was enhanced by prior incubation with indomethacin (10 mu M), whereas in endothelium-denuded preparatio ns an unaltered response was found. The present results indicate that L-T-4-induced relaxation is established by an indirect effect via the endothelium and by a direct effect on vascular smooth muscle cells, po ssibly by influencing calcium fluxes. Because vascular relaxation is e stablished at supraphysiologic concentrations (approximately 100 times the basal level) of thyroid hormone, it is concluded that the direct effect of thyroid hormone on mesenteric vascular smooth muscle cells a re not relevant for the in vivo situation.