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肾上腺切除大鼠的肾小球和血管心房利钠因子受体

Glomerular and vascular atrial natriuretic factor receptors in adrenalectomized rats.

作者信息

Cachofeiro V, Schiffrin E L, Cantin M, Garcia R

机构信息

Laboratory of Experimental Hypertension and Vasoactive Peptides, Clinical Research Institute of Montreal, Quebec, Canada.

出版信息

Am J Physiol. 1989 Jun;256(6 Pt 2):R1250-7. doi: 10.1152/ajpregu.1989.256.6.R1250.

Abstract

The renal and vascular responses to atrial natriuretic factor (ANF) and glomerular and vascular ANF receptors were studied in adrenalectomized (ADR) rats with or without deoxycorticosterone (DOC) or dexamethasone (Dexa) replacement therapy. As expected, adrenalectomy elicited hypotension, hemoconcentration, and increased plasma renin activity, but no changes in plasma levels of either ANF-(1-98) or ANF-(99-126) were detected. Dexa treatment decreased both ANF-(1-98) and ANF-(99-126), whereas DOC treatment increased only ANF-(1-98). The acute renal response to ANF and furosemide was reduced in ADR rats and partially restored either by steroid replacement or by raising blood pressure. The blunted natriuretic response to ANF in ADR rats was associated with an increased density of glomerular receptors. Norepinephrine-precontracted vascular strips from ADR rats were more sensitive to ANF (ED50: 1.7 x 10(-8) M) than those from sham-operated animals (ED50: 1.5 x 10(-7) M). However, vascular ANF receptor density in mesenteric vessels from ADR animals was decreased. Dexa treatment restored vascular response to that observed in sham-operated animals without a concomitant change in vascular receptor density. Because the presence of guanylate cyclase-coupled and noncoupled ANF receptor subtypes have been described in different tissues, we conclude that the apparent lack of correlation between the biological response to ANF and total binding of ANF to glomeruli or mesenteric artery membranes in ADR rats may be in part caused by a differential regulation of both receptor subtype populations.

摘要

在接受或未接受脱氧皮质酮(DOC)或地塞米松(Dexa)替代治疗的肾上腺切除(ADR)大鼠中,研究了肾脏和血管对心房利钠因子(ANF)的反应以及肾小球和血管ANF受体。正如预期的那样,肾上腺切除术引发了低血压、血液浓缩和血浆肾素活性增加,但未检测到血浆中ANF-(1-98)或ANF-(99-126)水平的变化。地塞米松治疗降低了ANF-(1-98)和ANF-(99-126)两者的水平,而脱氧皮质酮治疗仅增加了ANF-(1-98)。ADR大鼠对ANF和呋塞米的急性肾脏反应降低,通过类固醇替代或升高血压可部分恢复。ADR大鼠对ANF的利钠反应减弱与肾小球受体密度增加有关。来自ADR大鼠的去甲肾上腺素预收缩血管条对ANF(半数有效浓度:1.7×10⁻⁸ M)比假手术动物的血管条(半数有效浓度:1.5×10⁻⁷ M)更敏感。然而,ADR动物肠系膜血管中的血管ANF受体密度降低。地塞米松治疗使血管反应恢复到假手术动物中观察到的水平,而血管受体密度没有伴随变化。由于在不同组织中已描述了鸟苷酸环化酶偶联和非偶联的ANF受体亚型的存在,我们得出结论,ADR大鼠中对ANF的生物学反应与ANF与肾小球或肠系膜动脉膜的总结合之间明显缺乏相关性,可能部分是由两种受体亚型群体的差异调节引起的。

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