Hyperthyroidism enhances endothelium-dependent relaxation in the rat renal artery.
OBJECTIVE
Hyperthyroidism has pronounced effects on vascular function and endothelium-dependent relaxation. The aim of the present study was to identify mechanisms underlying hyperthyroidism-induced alterations in endothelial function in rats.


METHODS
Animals were subjected to either a single injection (36 h) or 8 weeks treatment with the thyroid hormone triiodothyronine (T3, i.p.). Vascular reactivity and agonist-induced hyperpolarization were studied in isolated renal arteries. Endothelial nitric oxide (NO) synthase expression and cyclic AMP accumulation were determined in aortic segments.


RESULTS
Endothelium-dependent relaxations to acetylcholine (ACh) were enhanced by T3 36 h after injection and after treatment for 8 weeks. Thirty-six hours after T3 application, relaxation mediated by the endothelium-derived hyperpolarizing factor (EDHF) and by endothelium-derived NO were significantly enhanced. After 8 weeks treatment with T3, however, EDHF-mediated relaxation was impaired, whereas NO-mediated relaxation remained enhanced. KCl- and ACh-induced hyperpolarizations were more pronounced in arteries from rats treated with T3 for 36 h compared to control, whereas in arteries from rats treated with T3 for 8 weeks both responses were attenuated. In rats treated for 36 h, vascular cyclic AMP levels were enhanced in the aorta and inhibition of protein kinase A attenuated EDHF-mediated relaxations of the renal artery without affecting responses in arteries from the control group. In the aorta from rats treated with T3 for 8 weeks, the expression of the endothelial NO synthase was markedly up-regulated (463+/-68%).


CONCLUSIONS
These data indicate that short-term treatment with T3 increases endothelium-dependent relaxation, most probably by increasing vascular cyclic AMP content. Following treatment with T3 for 8 weeks, expression of the endothelial NO synthase was enhanced. During this phase, NO appears to be the predominant endothelium-derived vasodilator.
Büssemaker
E
E
Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Theodor-Stern-Kai 7, D-60596 Frankfurt am Main, Germany.
Popp
R
R
Fisslthaler
B
B
Larson
C M
CM
Fleming
I
I
Busse
R
R
Brandes
R P
RP
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004008:Diclofenac / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D006980:Hyperthyroidism / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D012077:Renal Artery / Q000378:metabolism*; D014284:Triiodothyronine; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
D001685:Biological Factors; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D014284:Triiodothyronine; D004008:Diclofenac; D009569:Nitric Oxide; D011189:Potassium Chloride; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000109:Acetylcholine