Department of Physiology and Biophysics, Case Western Reserve University , Cleveland, Ohio.
Physiol Rev. 2019 Jan 1;99(1):235-309. doi: 10.1152/physrev.00055.2017.
The thick ascending limb plays a key role in maintaining water and electrolyte balance. The importance of this segment in regulating blood pressure is evidenced by the effect of loop diuretics or local genetic defects on this parameter. Hormones and factors produced by thick ascending limbs have both autocrine and paracrine effects, which can extend prohypertensive signaling to other structures of the nephron. In this review, we discuss the role of the thick ascending limb in the development of hypertension, not as a sole participant, but one that works within the rich biological context of the renal medulla. We first provide an overview of the basic physiology of the segment and the anatomical considerations necessary to understand its relationship with other renal structures. We explore the physiopathological changes in thick ascending limbs occurring in both genetic and induced animal models of hypertension. We then discuss the racial differences and genetic defects that affect blood pressure in humans through changes in thick ascending limb transport rates. Throughout the text, we scrutinize methodologies and discuss the limitations of research techniques that, when overlooked, can lead investigators to make erroneous conclusions. Thus, in addition to advancing an understanding of the basic mechanisms of physiology, the ultimate goal of this work is to understand our research tools, to make better use of them, and to contextualize research data. Future advances in renal hypertension research will require not only collection of new experimental data, but also integration of our current knowledge.
厚升支在维持水和电解质平衡方面起着关键作用。该节段在调节血压方面的重要性，可通过袢利尿剂或局部遗传缺陷对该参数的影响得到证明。厚升支产生的激素和因子具有自分泌和旁分泌作用，可将致高血压信号扩展到肾单位的其他结构。在这篇综述中，我们讨论了厚升支在高血压发展中的作用，它不是作为一个单独的参与者，而是在肾髓质丰富的生物学背景下发挥作用。我们首先概述了该节段的基本生理学和理解其与其他肾结构关系所需的解剖学考虑。我们探讨了在遗传性和诱导性高血压动物模型中厚升支发生的生理病理变化。然后，我们讨论了通过改变厚升支转运率影响人类血压的种族差异和遗传缺陷。在整篇文章中，我们仔细审查了方法，并讨论了研究技术的局限性，如果被忽视，可能会导致研究人员得出错误的结论。因此，除了深入了解生理学的基本机制外，这项工作的最终目标是了解我们的研究工具，更好地利用它们，并使研究数据具有背景意义。未来在肾性高血压研究方面的进展不仅需要收集新的实验数据，还需要整合我们现有的知识。
