RENAL ALPHA-ADRENERGIC RECEPTOR ABNORMALITY IN THE SPONTANEOUSLY HYPERTENSIVE RAT
RENAL ALPHA-ADRENERGIC RECEPTOR ABNORMALITY IN THE SPONTANEOUSLY HYPERTENSIVE RAT
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DOI：
10.1161/01.hyp.4.6.881
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发表时间：
1982-01-01
期刊：
影响因子：
8.3
通讯作者：
GANDLER, T
中科院分区：
文献类型：
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作者：
GRAHAM, RM;PETTINGER, WA;GANDLER, T
肾α-受体的激活肾上腺素能受体诱导血管收缩、近端肾小管对NA的重吸收和对肾素释放的抑制。在原发性高血压的动物模型和患者中，这些作用的过度程度不同。由于原发性高血压是由遗传决定的，因此，肾α-肾上腺素异常是一个非常重要的因素。在Okamoto-Aoki品系的自发性高血压大鼠（sr-SHR）和它们的易卒中变体（sp-SHR）中寻找肾上腺素能受体。总α-肾上腺素能受体浓度通过[~ 3 H]二氢麦角碱与肾膜部分结合的Scatchard分析来测定，发现与年龄和性别匹配的Wistar-Kyoto对照组相比，4、16和32周龄的雄性sr-SHR和16周龄的雌性sr-SHR的肾上腺素能受体浓度增加（P < 0.02）。在9周龄的sp-SHR肾组织中也有明显增加（P < 0.005）。进一步的研究表明，这种肾α-淀粉酶的增加肾上腺素能受体的增加完全是由于通过[3 H]育亨宾结合测量的α 2-受体的增加，而不是由于通过[3 H]哌唑嗪结合定量的α 1-受体的增加。任何高血压和血压正常的大鼠组之间的各种放射性配体的结合亲和力没有差异。4、9、16周龄SHR血浆去甲肾上腺素水平升高（P < 0.01），而32周龄高血压大鼠血浆去甲肾上腺素水平无明显变化。因此，在SHR的高血压发展过程中，高肾α 2-肾上腺素能受体数目与血浆去甲肾上腺素浓度的显著增加相关联。通过介导增强的受体偶联反应，例如增加的近端肾小管Na重吸收，肾α-Na的这种异常可被抑制。肾上腺素能受体可能参与导致SHR高血压的部分或全部病理生理紊乱。
Activation of renal .alpha.-adrenergic receptors induces vasoconstriction, proximal tubular reabsorption of NA and inhibition of renin release. Excesses of these effects are present in varying degrees in animal models of, and in patients with essential hypertension. Since essential hypertension is genetically determined, abnormalities of renal .alpha.-adrenergic receptors in the Okamoto-Aoki strain of spontaneously hypertensive rats (sr-SHR) and their stroke-prone variant (sp-SHR ) were sought. Total .alpha.-adrenergic receptor concentrations were determined by Scatchard analysis of [3H]dihydroergocryotine binding to a renal membrane fraction and were found to be increased (P < 0.02) in male sr-SHR at 4, 16 and 32 wk of age and in female sr-SHR at 16 wk of age as compared to age- and sex-matched Wistar-Kyoto controls. They were also increased in 9-wk-old sp-SHR renal membranes (P < 0.005). Further studies revealed that this increase in renal .alpha.-adrenergic receptors was due entirely to an increase in .alpha.2-receptors as measured by [3H]yohimbine binding rather than to an increase in .alpha.1-receptors as quantitated by [3H]prazosin binding. No difference in binding affinities of the various radioligands could be demonstrated between any of the hypertensive and normotensive groups of rats. Plasma norepinephrine levels were elevated (P < 0.01) in the 4-, 9- and 16-wk-old SHR, but not in the 32-wk-old hypertensive rats. Thus, high renal .alpha.2-adrenergic receptor number is coupled with a significant increase in plasma norepinephrine concentrations during the development of hypertension in SHR. By mediating an enhanced receptor-coupled response, such as increased proximal tubular Na reabsorption, this abnormality of renal .alpha.-adrenergic receptors may contribute to some or all of the pathophysiologic derangements leading to hypertension in SHR.