title: The influence of hyperthyroidism on pharmacologically induced contractions of isolated resistance arteries.
abstract: We investigated the effect of hyperthyroidism on the responses of small mesenteric resistance arteries to several contractile and dilator agents. Hyperthyroidism was established by feeding rats for 28 days with 5 mg/kg L-thyroxine-containing rat chow. This treatment produced a stable hyperthyroid state, as indicated by the increased serum T4 levels (236 +/- 7 vs. 60 +/- 2; T4-treated vs. control). Preparations of small mesenteric arteries were mounted in an isometric wire myograph. Subsequently, concentration-effect curves were determined for K+, Ca2+, methoxamine, phenylephrine, 5-hydroxytryptamine (5-HT), 9,11-dideoxy-11 alpha, 9 alpha-epoxymethano-prostaglandin F2 alpha (U46619), methacholine and nitroprusside. Our results indicate that hyperthyroidism does not induce major changes in the sensitivity of isolated resistance vessels to K+, Ca+, the alpha-adrenoceptor agonist, methacholine and nitroprusside. Furthermore, neither the affinity of alpha-receptors for methoxamine, nor the alpha-receptor reserve was influenced by the hyperthyroid state of the animal. A clearly sensitizing influence of hyperthyroidism was found for the vasoconstrictor effects of both 5-HT (6.57 +/- 0.04 vs. 6.29 +/- 0.06; hyperthyroid vs. control) and the thromboxane A2 receptor agonist U46619 (6.78 +/- 0.13 vs. 6.30 +/- 0.09; hyperthyroid vs. control). Sensitization to both 5-HT and U46619 was abolished in the presence of N omega-nitro-L-arginine methylester HCl (L-NAME, 0.1 mM). 5-HT-induced contractions in vessels from hyperthyroid rats were diminished by prior incubation with indomethacin (10 microM). The present results indicate that during hyperthyroidism resistance vessels are sensitized to both 5-HT and U46619. This sensitization involves the nitric oxide/L-arginine pathway and probably also certain steps in the cyclooxygenase pathway.
authors: Department of Pharmacotherapy, University of Amsterdam, Netherlands.
authors: J
authors: J
authors: Zwaveling
authors: E A
authors: EA
authors: Prins
authors: M A
authors: MA
authors: Maas
authors: M
authors: M
authors: Pfaffendorf
authors: P A
authors: PA
authors: Van Zwieten
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D006439:Hemodynamics; D006980:Hyperthyroidism / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000503:physiopathology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D000316:Adrenergic alpha-Agonists; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D012701:Serotonin; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid