Singh G, Sharma A C, Thompson E B, Gulati A
Department of Pharmaceutics and Pharmacodynamics, University of Illinois at Chicago 60612.
Life Sci. 1994;54(24):1901-8. doi: 10.1016/0024-3205(94)90148-1.
Endothelin (ET) mechanisms were studied in hyper- and hypo-thyroid states in rats. Hyperthyroidism was induced by daily administration of thyroxine (0.1 mg/kg, i.p.) for 8 weeks, while hypothyroidism was induced by daily administration of methimazole (10 mg/kg, i.p.) for 8 weeks. The concentration of endogenous ET-1 was determined in the kidneys using radioimmunoassay. Systemic hemodynamics and renal blood circulation was measured using a radioactive microsphere technique. A significant increase in systolic and diastolic blood pressure, heart rate and cardiac output was observed in hyperthyroid rats as compared to eu- and hypo-thyroid rats. Total peripheral resistance was found to be similar in eu-, hyper- and hypo-thyroid rats. The endogenous concentration of ET-1 in the kidneys was significantly lower in hyper- as compared to eu- and hypo-thyroid rats. The blood flow to the kidneys was significantly increased in hyper- as compared to eu- and hypo-thyroid rats. Infusion of ET-1 (100 ng/kg/min i.v. for 45 min) produced a significant decrease in blood flow to the kidneys of eu-, hyper- and hypo-thyroid rats. The decrease in blood flow was similar in eu-, hyper- and hypo-thyroid rats, indicating that the response of renal blood vessels to exogenous ET-1 is not altered during thyroid dysfunction. Since endogenous ET-1 is involved in the regulation of vascular tone, it may be concluded that in hyper-thyroid rats decrease in concentration of the renal ET-1 could be contributing to an increase in blood flow to the kidney.
研究了大鼠甲状腺功能亢进和减退状态下的内皮素（ET）机制。通过每天腹腔注射甲状腺素（0.1mg/kg）持续8周诱导甲状腺功能亢进，而通过每天腹腔注射甲巯咪唑（10mg/kg）持续8周诱导甲状腺功能减退。使用放射免疫分析法测定肾脏中内源性ET-1的浓度。使用放射性微球技术测量全身血流动力学和肾血液循环。与甲状腺功能正常和减退的大鼠相比，甲状腺功能亢进的大鼠收缩压、舒张压、心率和心输出量显著增加。发现甲状腺功能正常、亢进和减退的大鼠总外周阻力相似。与甲状腺功能正常和减退的大鼠相比，甲状腺功能亢进的大鼠肾脏中ET-1的内源性浓度显著降低。与甲状腺功能正常和减退的大鼠相比，甲状腺功能亢进的大鼠肾血流量显著增加。静脉注射ET-1（100ng/kg/min，持续45分钟）使甲状腺功能正常、亢进和减退的大鼠肾血流量显著减少。甲状腺功能正常、亢进和减退的大鼠血流量减少相似，表明甲状腺功能障碍期间肾血管对外源性ET-1的反应未改变。由于内源性ET-1参与血管张力的调节，因此可以得出结论，在甲状腺功能亢进的大鼠中，肾脏ET-1浓度的降低可能导致肾血流量增加。
