The direct effects of thyroid hormones on rat mesenteric resistance arteries.
The direct relaxant effects of thyroid hormones on mesenteric resistance vessels were investigated using an isometric wire myograph. Both the L- and the D-isomers of thyroxine (T4) and triiodothyronine (T3) were studied. In contrast with the long-term effects of thyroid hormones, both T4 enantiomers proved more potent in inducing vascular relaxation than the two T3 enantiomers. The interaction between thyroid hormones and calcium-induced contractions was studied. T4 concentration dependently inhibited the Ca2+ induced contractions, showing noncompetitive interaction. Furthermore, we investigated whether the endothelium was involved in the relaxant effect to L-T4. The T4 induced relaxation proved impaired by prior incubation with the nitric oxide (NO) inhibitor N-omega-nitro-L-arginine methylester HCl (L-NAME, 0.1 microM), indicating that T4 is able to stimulate the production of endothelium-derived NO. L-T4-induced relaxation was enhanced by prior incubation with indomethacin (10 microM), whereas in endothelium-denuded preparations an unaltered response was found. The present results indicate that L-T4-induced relaxation is established by an indirect effect via the endothelium and by a direct effect on vascular smooth muscle cells, possibly by influencing calcium fluxes. Because vascular relaxation is established 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 are not relevant for the in vivo situation.
Zwaveling
J
J
Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
Pfaffendorf
M
M
van Zwieten
P A
PA
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D013974:Thyroxine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014284:Triiodothyronine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects*
D014284:Triiodothyronine; D019001:Nitric Oxide Synthase; D013974:Thyroxine; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester