I Kid(ney) You Not...Natriuretic Peptides Which Promote Natriuresis but Not Hypotension.
I Kid(ney) You Not...Natriuretic Peptides Which Promote Natriuresis but Not Hypotension.
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我肾你不...利尿钠肽促进尿钠排泄而不是低血压。
DOI：
10.1161/circresaha.119.315129
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发表时间：
2019
影响因子：
20.1
通讯作者：
Blanton,RobertM
中科院分区：
文献类型：
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作者：
Blanton,RobertM
当然，在不同类型肾功能不全的人身上。最后，作者仔细研究了他们设计的NP对急性肾脏生理的影响，但对长期肾功能的影响尚不清楚。未来的研究有望回答这些临床相关的问题。虽然这项研究的重点是临床前手术模型的肾功能，但研究结果具有重要的心血管意义。肾功能不全和容量超载仍然是心力衰竭的主要后果。然而，传统的利尿剂减少容量超载的策略往往被证明是不够的，或者最终导致进一步的肾功能障碍，这是一种被称为心肾综合征的疾病。10使用奈西立肽等合成NPs来改善心衰患者的心输出量，从而改善肾灌注的替代策略经常会导致限制性低血压6，并且在这种情况下没有改善结果。因此，评估CRRL269和其他创新NPs作为心力衰竭肾功能障碍和容量过载的潜在血流动力学中性治疗的效果将提供信息。最后，作者证明CRRL269不仅在肾组织中增强cGMP，而且在血浆和尿液中增强cGMP。其他np调节药物，如耐普利素抑制剂，似乎也增加细胞外cGMP。为什么作为细胞内第二信使的cGMP在细胞外空间受到调节，这可能有什么临床和生物学意义？同时，本研究为解析NPs和下游cGMP-PKG信号通路的生物学效应迈出了重要的一步。而且，这项研究支持了一个更大的概念，即理解生理过程背后的基本生物学可以直接导致心血管（和心肾）疾病患者的新治疗策略。
1412 Circulation Research May 10, 2019 of course, in humans with different types of renal dysfunction. Finally, the authors carefully studied the effects of their designer NP on acute renal physiology, but the effects on longerterm kidney function remain unclear. Future investigations will hopefully answer these clinically relevant questions. Although this study focused on renal function in a preclinical surgical model, the findings have important cardiovascular implications. Renal dysfunction and volume overload remain major consequences of heart failure. However, conventional strategies to reduce volume overload with diuretics often prove inadequate or ultimately contribute to further renal dysfunction, one form of a spectrum of conditions known as cardiorenal syndrome. 10 Alternative strategies using synthetic NPs like nesiritide to improve cardiac output and thus renal perfusion in heart failure frequently induce limiting hypotension, 6 and have not improved outcomes in this condition. Thus, it will be informative to evaluate the effects of CRRL269, and other innovative NPs, as potentially hemodynamically neutral treatments of renal dysfunction and volume overload in the setting of heart failure. Finally, the authors demonstrated that CRRL269 augments cGMP not only in renal tissue but also in the plasma and urine. Other NP-modulating drugs, like neprilysin inhibitors, also appear to increase extracellular cGMP. 11 Why does cGMP, which functions as an intracellular second messenger, become regulated in the extracellular space, and what might be the clinical and biological significance of this? In the meantime, the current study represents an important step in parsing out the biological effects of NPs and downstream cGMP-PKG signaling. And, this study supports the greater concept that understanding the basic biology underlying physiological processes can lead directly to novel therapeutic strategies for patients with cardiovascular (and cardiorenal) disease.