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长期给予乙醇对Wistar-Kyoto大鼠和自发性高血压大鼠脑干α₂受体结合的影响。

Effect of long-term ethanol feeding on brainstem alpha(2)-receptor binding in Wistar-Kyoto and spontaneously hypertensive rats.

作者信息

El-Mas M M, Abdel-Rahman A A

机构信息

Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858-4353, USA.

出版信息

Brain Res. 2001 May 11;900(2):324-8. doi: 10.1016/s0006-8993(01)02316-2.

Abstract

Our previous studies have shown that ethanol attenuates baroreflex function in Wistar-Kyoto (WKY) but not in spontaneously hypertensive rats (SHRs). The present study determined the effects of chronic ethanol administration on alpha(2)-binding sites in brainstem areas that modulate baroreflexes. In vitro autoradiography was utilized to evaluate the effect of a 3-month ethanol feeding on the density (B(max)) and affinity (K(D)) of alpha(2)-adrenoceptors in the middle (mNTS) and rostral (rNTS) portions of the nucleus tractus solitarius of SHRs and WKY rats. Autoradiographic examination of brainstem sections preincubated with [125I]p-iodoclonidine revealed no inter-strain differences in alpha(2)-binding in control rats. Ethanol feeding caused strain-dependent changes in alpha(2)-binding activity, which comprised significant (P<0.05) decreases in the density of alpha(2)-binding sites in both areas of the NTS in SHRs versus no effect in WKY rats. These findings do not favor a role for brainstem alpha(2)-adrenoceptors in ethanol-induced attenuation of baroreflexes. Interestingly, the ethanol-evoked reduction in the NTS alpha(2)-receptor density in SHRs may explain reported findings that ethanol abolishes the hypotensive effect of the alpha(2)-adrenoceptor agonist clonidine in this rat model.

摘要

我们之前的研究表明,乙醇会减弱Wistar-Kyoto(WKY)大鼠的压力反射功能,但不会减弱自发性高血压大鼠(SHR)的压力反射功能。本研究确定了长期给予乙醇对调节压力反射的脑干区域α₂结合位点的影响。利用体外放射自显影技术评估了为期3个月的乙醇喂养对SHR和WKY大鼠孤束核中部(mNTS)和吻侧(rNTS)部分α₂肾上腺素能受体密度(Bmax)和亲和力(KD)的影响。用[¹²⁵I]对碘氯苄胍预孵育的脑干切片的放射自显影检查显示,对照大鼠的α₂结合在品系间没有差异。乙醇喂养导致α₂结合活性出现品系依赖性变化,即SHR的NTS两个区域的α₂结合位点密度显著降低(P < 0.05),而WKY大鼠则无此效应。这些发现不支持脑干α₂肾上腺素能受体在乙醇诱导的压力反射减弱中起作用。有趣的是,乙醇引起的SHR中NTSα₂受体密度降低可能解释了已报道的乙醇消除该大鼠模型中α₂肾上腺素能受体激动剂可乐定的降压作用这一发现。

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