The influence of hyperthyroidism on pharmacologically induced contractions of isolated resistance arteries.
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.
Zwaveling
J
J
Department of Pharmacotherapy, University of Amsterdam, Netherlands.
Prins
E A
EA
Maas
M A
MA
Pfaffendorf
M
M
Van Zwieten
P A
PA
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*
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