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实验性高血压中肾微血管肌源性反应性的改变

Altered myogenic responsiveness of the renal microvasculature in experimental hypertension.

作者信息

Hayashi K, Epstein M, Saruta T

机构信息

Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.

出版信息

J Hypertens. 1996 Dec;14(12):1387-401. doi: 10.1097/00004872-199612000-00002.

Abstract

Recent investigations have delineated the renal microvascular responsiveness to pressure, by using isolated afferent arterioles, juxtamedullary nephrons, and isolated perfused hydronephrotic kidneys. Both afferent arterioles and interlobular arteries (ILA) manifest pressure-dependent vasoconstrictor responses to elevated renal arterial pressure. Several recent studies have indicated that the afferent arteriole adjacent to the glomerulus constricts primarily in response to tubuloglomerular feedback signals, whereas the afferent arteriole near the ILA is under the dominant influence of myogenic tone. Furthermore, the responsiveness of the ILA to pressure is dependent on the basal diameter, with the smaller diameter (distal) segments demonstrating more marked responses than do the larger (proximal) segments. The myogenic afferent arteriolar response is shifted to higher perfusion pressure in spontaneously hypertensive rat (SHR) kidneys, and blunted both in Dahl salt-sensitive rats and in Goldblatt renal hypertensive rats. This altered responsiveness of the afferent arteriole may account for the alterations in renal blood flow autoregulation, namely, resetting toward higher pressures in SHR, and impairment in Dahl salt-sensitive rats and Goldblatt hypertensive rats Distal ILA segments vasoconstricted similarly in response to pressure both in SHR and in Wistar-Kyoto rats (WKY), whereas proximal ILA segments did not exhibit vasoconstriction in either strain. The intermediate ILA segment from SHR kidneys manifests more prominent myogenic vasoconstriction than does that from WKY rat kidneys. The enhanced myogenic responsiveness of the intermediate ILA segment may act in concert with afferent arteriolar vasoconstriction to prevent glomerular hypertension in superficial nephrons. Finally, the myogenic vasoconstriction of renal microvessels is mediated in part by voltage-dependent calcium channels, and the altered myogenic response may be associated with modified activity of voltage-dependent calcium channels. Thus, the myogenic preglomerular tone constitutes a pivotal determinant of renal autoregulation, and teleologically may also play an important role in protecting glomeruli from barotrauma in hypertension, whereas the functional myogenic element is soon reinforced by an element of "structural autoregulation' of preglomerular resistance vessels.

摘要

最近的研究通过使用分离的入球小动脉、近髓肾单位和分离灌注的积水肾,描绘了肾微血管对压力的反应性。入球小动脉和小叶间动脉(ILA)对升高的肾动脉压力均表现出压力依赖性血管收缩反应。最近的几项研究表明,与肾小球相邻的入球小动脉主要对肾小管-肾小球反馈信号作出收缩反应,而靠近ILA的入球小动脉受肌源性张力的主导影响。此外,ILA对压力的反应性取决于基础直径,直径较小(远端)的节段比直径较大(近端)的节段表现出更明显的反应。在自发性高血压大鼠(SHR)肾脏中,肌源性入球小动脉反应向更高灌注压力偏移,而在Dahl盐敏感大鼠和Goldblatt肾性高血压大鼠中则减弱。入球小动脉这种改变的反应性可能解释了肾血流自动调节的改变,即SHR中向更高压力的重新设定,以及Dahl盐敏感大鼠和Goldblatt高血压大鼠中的受损情况。SHR和Wistar-Kyoto大鼠(WKY)的远端ILA节段对压力的血管收缩反应相似,而近端ILA节段在两种品系中均未表现出血管收缩。SHR肾脏的中间ILA节段比WKY大鼠肾脏的表现出更明显的肌源性血管收缩。中间ILA节段增强的肌源性反应性可能与入球小动脉血管收缩协同作用,以防止浅表肾单位的肾小球高血压。最后,肾微血管的肌源性血管收缩部分由电压依赖性钙通道介导,改变的肌源性反应可能与电压依赖性钙通道活性的改变有关。因此,肌源性球前张力是肾自动调节的关键决定因素,从目的论角度来看,在高血压中保护肾小球免受气压伤方面也可能起重要作用,而功能性肌源性成分很快会被球前阻力血管的“结构自动调节”成分加强。

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