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长期给予肼屈嗪对自发性高血压大鼠中由突触前α和β肾上腺素能受体介导的肾上腺素能神经传递改变的影响。

Effect of chronically administered hydralazine on altered adrenergic neurotransmission mediated by presynaptic alpha- and beta-adrenoceptors in spontaneously hypertensive rats.

作者信息

Takata Y, Mochizuki S, Kato H

机构信息

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.

出版信息

J Pharmacobiodyn. 1990 Sep;13(9):565-73. doi: 10.1248/bpb1978.13.565.

Abstract

The effects of chronically administered hydralazine on adrenergic neurotransmission were evaluated in the perfused mesenteric artery of spontaneously hypertensive rats (SHR) preloaded with [3H]norepinephrine. The 3H overflow evoked by periarterial nerve stimulation (PNS, 2-32 Hz) was greater in both young (5-week-old) and adult (13-week-old) ages of SHR in comparison with age-matched Wistar Kyoto rats (WKY). Hydralazine treatment, which prevented the development of hypertension, attenuated the increased 3H overflow evoked by PNS in SHR. At adult age, the logarithmic value for the concentration (nM) of salbutamol to cause a 20% enhancement of the evoked 3H overflow was significantly smaller in SHR than in WKY. The increased sensitivity of presynaptic beta-adrenoceptors in SHR was reduced by hydralazine treatment. The concentration-response curve of the facilitation of the evoked 3H overflow caused by salbutamol in hydralazine-treated SHR lay between the curves in SHR and WKY. No significant difference in the inhibitory effects of xylazine on the PNS-evoked 3H overflow was found among SHR, hydralazine-treated SHR and WKY. At young age, presynaptic alpha- and beta-adrenoceptors were supersensitive in SHR. The results suggest that an altered adrenergic neurotransmission mediated by presynaptic beta-adrenoceptors in adult SHR is partially improved by chronic hydralazine administration, this accounting for the attenuation of the increased norepinephrine release observed in hydralazine-treated SHR.

摘要

在预先用[3H]去甲肾上腺素加载的自发性高血压大鼠(SHR)的灌注肠系膜动脉中,评估了长期给予肼屈嗪对肾上腺素能神经传递的影响。与年龄匹配的Wistar Kyoto大鼠(WKY)相比,在年轻(5周龄)和成年(13周龄)的SHR中,动脉周围神经刺激(PNS,2 - 32Hz)引起的3H溢出量更大。预防高血压发展的肼屈嗪治疗减弱了SHR中PNS引起的3H溢出量增加。在成年时,沙丁胺醇浓度(nM)对数导致诱发的3H溢出量增加20%时,SHR中的该值显著小于WKY。肼屈嗪治疗降低了SHR中突触前β - 肾上腺素能受体增加的敏感性。在肼屈嗪治疗的SHR中,沙丁胺醇引起的诱发3H溢出促进作用的浓度 - 反应曲线介于SHR和WKY的曲线之间。在SHR、肼屈嗪治疗的SHR和WKY之间,未发现赛拉嗪对PNS诱发的3H溢出的抑制作用有显著差异。在幼年时,SHR中的突触前α和β肾上腺素能受体超敏。结果表明,成年SHR中由突触前β肾上腺素能受体介导的肾上腺素能神经传递改变通过长期给予肼屈嗪得到部分改善,这解释了在肼屈嗪治疗SHR中观察到的去甲肾上腺素释放增加的减弱。

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