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肾性高血压大鼠的肾上腺素能受体与主动脉平滑肌反应性增强

Adrenergic receptors and increased reactivity of aortic smooth muscle in renal hypertensive rats.

作者信息

Lin C I, Lu H H, Lin K Y

出版信息

J Auton Nerv Syst. 1982 May;5(3):253-64. doi: 10.1016/0165-1838(82)90069-8.

Abstract

The contractile responses of aortic smooth muscle and the dissociation constant (Ka) of the norepinephrine (NE) acting on alpha-adrenergic receptors in isolated thoracic aorta from normotensive and renal hypertensive rats were studied. Male Wistar rats were made hypertensive by uninephrectomy with figure-of-eight ligatures around the contralateral kidney. Two to three weeks after operation, the arterial systolic pressure for sham-operated rats was 123 +/- 2, and that for hypertensive rats was 164 +/- 4 mm Hg. Spontaneous rhythmic contractions of aortic rings, which were potentiated by low [Na]o and abolished by nifedipine (10(-6) - 10(-5) M), were observed in 4 out of 18 hypertensive rats. Aortic rings from normotensive rats showed no spontaneous rhythmicity. Although rhythmic phasic contractions could be induced in normotensive tissues by NE or caffeine in the presence of NE, tissues of hypertensive rats responded more readily. Furthermore, the threshold and the ED50 for tonic contractile response to NE was lower in hypertensive aortic rings than in the rings obtained from normotensive aortas. The Ka of NE acting on alpha-adrenergic receptors was derived from concentration-response data for NE before and after irreversible blockade of a fraction of the receptors with dibenamine (1-2 X 10(-7) M) in the presence of cocaine and propranolol. Mean Kas obtained were 5.58 +/- 0.42 X 10(-7) and 2.12 +/- 0.28 X 10(-7) M for normotensive and hypertensive rats, respectively. The increased contractile responses of the hypertensive aorta may be explained, at least partially, by a higher resting [Ca]i and a greater affinity of NE acting on the alpha-adrenergic receptors.

摘要

研究了正常血压大鼠和肾性高血压大鼠离体胸主动脉中主动脉平滑肌的收缩反应以及去甲肾上腺素(NE)作用于α-肾上腺素能受体的解离常数(Ka)。雄性Wistar大鼠通过对侧肾脏的八字结扎单侧肾切除制成高血压模型。术后两到三周,假手术大鼠的动脉收缩压为123±2,高血压大鼠为164±4 mmHg。在18只高血压大鼠中有4只观察到主动脉环的自发节律性收缩,这种收缩在低[Na]o时增强,在硝苯地平(10(-6)-10(-5) M)作用下消失。正常血压大鼠的主动脉环未显示出自发节律性。虽然在存在NE的情况下,NE或咖啡因可在正常血压组织中诱导节律性相收缩,但高血压大鼠的组织反应更迅速。此外,高血压主动脉环对NE的强直性收缩反应的阈值和ED50低于正常血压主动脉环。在可卡因和普萘洛尔存在的情况下,用双苄胺(1-2×10(-7) M)不可逆地阻断一部分受体前后,NE作用于α-肾上腺素能受体的Ka由NE的浓度-反应数据推导得出。正常血压大鼠和高血压大鼠获得的平均Kas分别为5.58±0.42×10(-7)和2.12±0.28×10(-7) M。高血压主动脉收缩反应的增强至少部分可以用较高的静息[Ca]i和NE对α-肾上腺素能受体的更大亲和力来解释。

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