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自发性高血压大鼠离体肾脏生物胺的形成

Formation of biogenic amines by isolated kidneys of spontaneously hypertensive rats.

作者信息

Stier C T, Brewer T F, Dick L B, Wynn N, Itskovitz H D

出版信息

Life Sci. 1986 Jan 6;38(1):7-14. doi: 10.1016/0024-3205(86)90268-7.

Abstract

Kidneys form dopamine (DA) from L-dopa and serotonin from L-5-hydroxytryptophan (L-5-HTP) via aromatic L-amino acid decarboxylase. We compared the ability of isolated perfused kidneys from adult (20-week-old) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) to form these biogenic amines. Renal vascular resistance (RVR) was greater in perfused kidneys from SHR (n = 10) than WKY (n = 8) (p less than 0.01). Slight decreases in RVR were observed during L-dopa infusion but these were unrelated to DA formation. L-Dopa infusion was associated with greater DA output in SHR than WKY in both the renal venous and urinary effluents although the latter did not achieve statistical significance. L-5-HTP increased RVR to a greater degree in SHR than WKY kidneys. This was associated with larger quantities of serotonin in the urinary and venous effluents and greater pressor responses to exogenous serotonin in SHR than WKY kidneys; however, either parameter alone was not significantly increased. Our findings do not support a deficiency of intrarenal DA formation as a pathogenic factor for hypertension in SHR. Biogenic amine formation is as great if not greater in SHR than WKY kidneys and appears to contribute largely to the greater increases in renal resistance seen in SHR kidneys on infusion of L-5-HTP. Enhanced renal serotonin formation may elevate blood pressure, whereas enhanced renal DA formation would favor blood pressure lowering, perhaps as a compensatory mechanism.

摘要

肾脏通过芳香族L-氨基酸脱羧酶将左旋多巴转化为多巴胺(DA),并将L-5-羟色氨酸(L-5-HTP)转化为5-羟色胺。我们比较了成年(20周龄)自发性高血压大鼠(SHR)和正常血压的Wistar-Kyoto大鼠(WKY)分离灌注肾脏形成这些生物胺的能力。SHR(n = 10)灌注肾脏的肾血管阻力(RVR)高于WKY(n = 8)(p < 0.01)。在输注左旋多巴期间观察到RVR略有下降,但这些与DA的形成无关。尽管后者未达到统计学意义,但在肾静脉和尿液流出物中,SHR输注左旋多巴后的DA产量均高于WKY。L-5-HTP使SHR肾脏的RVR升高程度大于WKY肾脏。这与尿液和静脉流出物中5-羟色胺的含量增加以及SHR肾脏对外源性5-羟色胺的升压反应大于WKY肾脏有关;然而,单独的任何一个参数都没有显著增加。我们的研究结果不支持肾内DA形成不足是SHR高血压致病因素的观点。SHR肾脏中生物胺的形成即使不超过WKY肾脏也与之相当,并且在输注L-5-HTP时,似乎在很大程度上导致了SHR肾脏中肾阻力的更大增加。肾脏5-羟色胺形成增强可能会升高血压,而肾脏DA形成增强可能有利于降低血压,这可能是一种代偿机制。

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