Thyroid hormones directly interact with vascular smooth muscle strips.
The thyroid hormones have direct effects on vascular smooth muscle and are potent vasorelaxants. In the present study, the effects of d- and l-thyroxine (d-T4 and l-T4), 3,5,3'-triiodo-d-thyronine (d-T3), and 3,5,3'-triiodo-l-thyronine (l-T3) on the isolated mesenteric artery of the rabbit and superprecipitation of actomyosin from bovine aorta were examined. These thyroid hormones dose dependently relaxed vascular strips previously contracted with 50 mM KCl in the presence of phentolamine (1 microM), propranolol (1 microM), and atropine (0.3 microM), and the order of the inhibitory potency was l-T4 greater than d-T4 greater than l-T3 greater than d-T3 for the contraction. Pretreatment with l-T4 (10 and 30 microM) inhibited the contractile response concomitant with the inhibition of the 20,000-Da myosin light chain phosphorylation, without significant suppression of the increase in La3+-resistant 45Ca influx and uptake (5 and 30 min) induced by 50 mM KCl, suggesting that the inhibitory effect of l-T4 may not be primarily related to Ca2+ entry through the voltage-dependent Ca2+ channel. The l-T4 (10 and 30 microM) showed noncompetitive antagonism against the Ca2+-induced contraction in the high K+-depolarized vascular strips. Superprecipitation of actomyosin was inhibited by the addition of l-T4, in a dose-dependent manner, and calmodulin (1 microgram/ml) partly reversed the inhibitory effect of l-T4. Thyroid hormones were found to inhibit Ca2+/calmodulin-dependent smooth muscle myosin light chain kinase, and the Ki value for l-T4 was 2.5 microM. Although the concentrations of l-T4 used in this study are high, relative to circulating physiological levels, thyroid hormones act directly at the blood vessel wall to cause inhibition of the contractile process in vascular smooth muscle in vitro. Modulation of the 20,000-Da myosin light chain phosphorylation via the inhibition of myosin light chain kinase activity may at least in part contribute to the inhibitory effect of l-T4.
Ishikawa
T
T
Department of Pharmacology, Nagoya University School of Medicine, Japan.
Chijiwa
T
T
Hagiwara
M
M
Mamiya
S
S
Hidaka
H
H
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D007811:Lanthanum / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D015879:Myosin Subfragments; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D011817:Rabbits; D013974:Thyroxine / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology*; D014285:Triiodothyronine, Reverse / Q000494:pharmacology*
D015879:Myosin Subfragments; D010446:Peptide Fragments; D014284:Triiodothyronine; D014285:Triiodothyronine, Reverse; D011189:Potassium Chloride; D007811:Lanthanum; D011494:Protein Kinases; D009219:Myosin-Light-Chain Kinase; D009218:Myosins; D009543:Nifedipine; D013974:Thyroxine; D002118:Calcium