内皮素 B 受体缺乏症大鼠模型中肾传入神经活动升高。

IF 3.7 2区 医学 Q1 PHYSIOLOGY American Journal of Physiology-renal Physiology Pub Date : 2023-08-01 Epub Date: 2023-06-22 DOI:10.1152/ajprenal.00064.2023
Bryan K Becker, Caroline M Grady, Alexa E Markl, Alfredo A Torres Rodriguez, David M Pollock
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引用次数: 0

摘要

肾脏神经一直是降低血压干预措施的一个有吸引力的目标;然而,肾脏传入(感觉)神经和传出交感神经在介导高血压方面的具体作用还没有得到很好的描述。一些研究表明,肾传入神经传递的交感兴奋信号会引起血压升高,而另一些研究则发现了交感抑制传入通路。这些交感抑制通路已被确定为通过内皮素 B(ETB)受体的激活对盐敏感性血压升高具有保护作用。我们假设,与转基因对照组相比,ETB 缺失(ETB-def)大鼠(除肾上腺素能组织外没有功能性 ETB 受体)缺乏适当的交感抑制,在高盐饮食后肾传入神经活性较低。我们发现,与转基因对照组相比,高盐喂养的 ETB 缺失动物离体肾盂对前列腺素 E2 这种生理刺激缺乏反应,但对辣椒素这种有害刺激却有同样的反应。令人惊讶的是,与转基因对照组相比,我们在正常和高盐饮食条件下观察到完整的 ETB-def 大鼠肾传入神经活动升高。ETB-def 大鼠先前已被证明具有更高的整体交感神经张力,我们还观察到在正常和高盐饮食条件下,ETB-def 大鼠的肾脏交感神经总活性高于转基因对照组。这些数据表明,ETB 受体是交感抑制性肾传入神经反射(肾上腺反射)的重要介质,在 ETB 缺乏的遗传大鼠模型中,交感兴奋性肾传入神经活动占主导地位,可能会导致高血压。缺乏内皮素 B 受体的大鼠传入神经活动增加,但对高盐饮食无反应。
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Elevated renal afferent nerve activity in a rat model of endothelin B receptor deficiency.

Renal nerves have been an attractive target for interventions aimed at lowering blood pressure; however, the specific roles of renal afferent (sensory) versus efferent sympathetic nerves in mediating hypertension are poorly characterized. A number of studies have suggested that a sympathoexcitatory signal conveyed by renal afferents elicits increases in blood pressure, whereas other studies identified sympathoinhibitory afferent pathways. These sympathoinhibitory pathways have been identified as protective against salt-sensitive increases in blood pressure through endothelin B (ETB) receptor activation. We hypothesized that ETB-deficient (ETB-def) rats, which are devoid of functional ETB receptors except in adrenergic tissues, lack appropriate sympathoinhibition and have lower renal afferent nerve activity following a high-salt diet compared with transgenic controls. We found that isolated renal pelvises from high salt-fed ETB-def animals lack a response to a physiological stimulus, prostaglandin E2, compared with transgenic controls but respond equally to a noxious stimulus, capsaicin. Surprisingly, we observed elevated renal afferent nerve activity in intact ETB-def rats compared with transgenic controls under both normal- and high-salt diets. ETB-def rats have been previously shown to have heightened global sympathetic tone, and we also observed higher total renal sympathetic nerve activity in ETB-def rats compared with transgenic controls under both normal- and high-salt diets. These data indicate that ETB receptors are integral mediators of the sympathoinhibitory renal afferent reflex (renorenal reflex), and, in a genetic rat model of ETB deficiency, the preponderance of sympathoexcitatory renal afferent nerve activity prevails and may contribute to hypertension.NEW & NOTEWORTHY Here, we found that endothelin B receptors are an important contributor to renal afferent nerve responsiveness to a high-salt diet. Rats lacking endothelin B receptors have increased afferent nerve activity that is not responsive to a high-salt diet.

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来源期刊
CiteScore
8.40
自引率
7.10%
发文量
154
审稿时长
2-4 weeks
期刊介绍: The American Journal of Physiology - Renal Physiology publishes original manuscripts on timely topics in both basic science and clinical research. Published articles address a broad range of subjects relating to the kidney and urinary tract, and may involve human or animal models, individual cell types, and isolated membrane systems. Also covered are the pathophysiological basis of renal disease processes, regulation of body fluids, and clinical research that provides mechanistic insights. Studies of renal function may be conducted using a wide range of approaches, such as biochemistry, immunology, genetics, mathematical modeling, molecular biology, as well as physiological and clinical methodologies.
期刊最新文献
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