Grassby P F, McNeill J H
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
J Pharmacol Exp Ther. 1988 Mar;244(3):1027-35.
The effect of hyperthyroidism was investigated on the sensitivity of rat aortic and mesenteric arteries to the contractile effects of biogenic amines, K+ and Ca++. Supersensitivity to norepinephrine, methoxamine and clonidine was observed in the mesenteric artery. Methoxamine and clonidine are immune to disposition by neuronal and extraneuronal uptake, and supersensitivity to norepinephrine persisted in the presence of hydrocortisone and desmethylimipramine, suggesting that the supersensitivity was postjunctional in origin. In addition, reserpine pretreatment induced supersensitivity to norepinephrine in control mesenteric arteries, but in hyperthyroid mesenteric arteries no further increase in sensitivity was observed after reserpine pretreatment supporting a postjunctional mechanism. In the aorta, a small increase in sensitivity was observed to norepinephrine, no supersensitivity was detected to methoxamine and supersensitivity to norepinephrine was not apparent in the presence of hydrocortisone, suggesting a prejunctional mechanism. The existence of a small prejunctional component in the mesenteric artery also was indicated, as incubation with hydrocortisone attenuated the degree of supersensitivity after thyroid hormone pretreatment. In the mesenteric artery, postjunctional supersensitivity also was observed to 5-hydroxytryptamine. However, no increase in sensitivity was observed to KCl or CaCl2 suggesting that the postjunctional supersensitivity was not due to an increase in the sensitivity of the contractile apparatus, and was specific for receptor-mediated effects of agonists.
研究了甲状腺功能亢进对大鼠主动脉和肠系膜动脉对生物胺、钾离子和钙离子收缩作用敏感性的影响。在肠系膜动脉中观察到对去甲肾上腺素、甲氧明和可乐定的超敏反应。甲氧明和可乐定不受神经元和非神经元摄取的影响，并且在氢化可的松和去甲丙咪嗪存在的情况下对去甲肾上腺素的超敏反应仍然存在，这表明超敏反应起源于节后。此外，利血平预处理可诱导对照肠系膜动脉对去甲肾上腺素的超敏反应，但在甲状腺功能亢进的肠系膜动脉中，利血平预处理后未观察到敏感性进一步增加，这支持了节后机制。在主动脉中，观察到对去甲肾上腺素的敏感性略有增加，未检测到对甲氧明的超敏反应，并且在氢化可的松存在的情况下对去甲肾上腺素的超敏反应不明显，这表明是节前机制。肠系膜动脉中也存在一个小的节前成分，因为与氢化可的松孵育可减弱甲状腺激素预处理后的超敏反应程度。在肠系膜动脉中，对5-羟色胺也观察到节后超敏反应。然而，未观察到对氯化钾或氯化钙的敏感性增加，这表明节后超敏反应不是由于收缩装置的敏感性增加，而是对激动剂受体介导的效应具有特异性。
