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大鼠醋酸脱氧皮质酮高血压模型中的血浆儿茶酚胺、去甲肾上腺素代谢及血管反应

Plasma catecholamines, noradrenaline metabolism and vascular response in desoxycorticosterone acetate hypertension of rats.

作者信息

Rascher W, Schömig A, Dietz R, Weber J, Gross F

出版信息

Eur J Pharmacol. 1981 Nov 5;75(4):255-63. doi: 10.1016/0014-2999(81)90552-5.

Abstract

Mineralocorticoid hypertension was induced in male Wistar rats by the injection of desoxycorticosterone acetate (DOCA) in oily solution (2 X 5 mg/kg daily for 7 days) and of desoxycorticosterone trimethylacetate in a microcrystalline suspension (15 mg/kg every third day for 4 weeks). A 1% NaCl solution or demineralized water was given as drinking fluid. Four weeks after the beginning of treatment, mean arterial blood pressure was 161 +/- 3.8 mmHg in DOCA-saline treated and 140 +/- 5.9 mmHg in DOCA-water-treated rats. Basal plasma levels of noradrenaline and adrenaline did not differ in conscious, unrestrained DOCA-treated rats and in control rats 3, 7 and 28 days after the beginning of hormone administration. Furosemide (50 mg/kg) caused within 30 min the same degree of diuresis and natriuresis in DOCA-treated and in control rats, but the plasma noradrenaline concentration in DOCA-treated rats rose to a higher level than in the controls. The isolated perfused hearts of rats which received DOCA for 7 and 28 days, respectively, had a reduced uptake of [3H]noradrenaline as compared to the controls. In isolated perfused hindlimb preparations from rats which had received DOCA for 7 days, the dose-response curve to noradrenaline but not that to KCl was shifted to the left. However, when DOCA and saline were given for 28 days, besides a higher sensitivity to noradrenaline an increased maximum response was observed with both noradrenaline and KCl. It is concluded that adrenergic tone is enhanced during the development of DOCA hypertension. Since the changes in the sympathetic nervous system in DOCA-water-treated rats, which had a less pronounced hypertension, were similar to those in DOCA-NaCl-treated rats, alterations in adrenergic vascular tone were not directly related to the level of the blood pressure.

摘要

通过向雄性Wistar大鼠注射醋酸脱氧皮质酮(DOCA)油溶液(每天2×5mg/kg,共7天)和微晶混悬液中的三甲基醋酸脱氧皮质酮(每三天15mg/kg,共4周)诱导盐皮质激素性高血压。给予1% NaCl溶液或去离子水作为饮用水。治疗开始四周后,DOCA-盐水处理组大鼠的平均动脉血压为161±3.8 mmHg,DOCA-水处理组大鼠为140±5.9 mmHg。在激素给药开始后的3、7和28天,清醒、未束缚的DOCA处理大鼠和对照大鼠的基础血浆去甲肾上腺素和肾上腺素水平无差异。呋塞米(50mg/kg)在30分钟内使DOCA处理大鼠和对照大鼠产生相同程度的利尿和利钠作用,但DOCA处理大鼠的血浆去甲肾上腺素浓度升至比对照组更高的水平。分别接受DOCA处理7天和28天的大鼠的离体灌注心脏,与对照组相比,[3H]去甲肾上腺素摄取减少。在接受DOCA处理7天的大鼠的离体灌注后肢制剂中,去甲肾上腺素的剂量-反应曲线向左移动,但氯化钾的曲线未移动。然而,当给予DOCA和盐水28天时,除了对去甲肾上腺素的敏感性增加外,去甲肾上腺素和氯化钾的最大反应均增加。结论是在DOCA高血压发展过程中肾上腺素能张力增强。由于DOCA-水处理组大鼠(高血压不太明显)的交感神经系统变化与DOCA-NaCl处理组大鼠相似,因此肾上腺素能血管张力的改变与血压水平无直接关系。

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