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双侧肾去神经对自发性高血压大鼠开环压力反射功能和尿排泄的影响。

Effects of bilateral renal denervation on open-loop baroreflex function and urine excretion in spontaneously hypertensive rats.

机构信息

Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka, Japan.

Department of Research Promotion and Management, National Cerebral and Cardiovascular Center, Osaka, Japan.

出版信息

Hypertens Res. 2024 Nov;47(11):3255-3266. doi: 10.1038/s41440-024-01883-5. Epub 2024 Sep 11.

Abstract

Bilateral renal denervation (RDN) decreases arterial pressure (AP) or delays the development of hypertension in spontaneously hypertensive rats (SHR), but whether bilateral RDN significantly modifies urine output function during baroreflex-mediated acute AP changes remains unknown. We quantified the relationship between AP and normalized urine flow (nUF) in SHR that underwent bilateral RDN (n = 9) and compared the results with those in sham-operated SHR (n = 9). Moreover, we examined the acute effect of an angiotensin II type 1 receptor blocker telmisartan (2.5 mg/kg) on the AP-nUF relationship. Bilateral RDN significantly decreased AP by narrowing the response range of the total arc of the carotid sinus baroreflex. The slopes of nUF versus the mean AP (in μL·min·kg·mmHg) in the sham and RDN groups under baseline conditions were 0.076 ± 0.045 and 0.188 ± 0.039, respectively; and those after telmisartan administration were 0.285 ± 0.034 and 0.416 ± 0.078, respectively. The effect of RDN on the nUF slope was marginally significant (P = 0.059), which may have improved the controllability of urine output in the RDN group. The effect of telmisartan on the nUF slope was significant (P < 0.001) in the sham and RDN groups, signifying the contribution of circulating or locally produced angiotensin II to determining urine output function regardless of ongoing renal sympathetic nerve activity.

摘要

双侧肾去神经支配(RDN)可降低自发性高血压大鼠(SHR)的动脉压(AP)或延缓高血压的发展,但双侧 RDN 是否显著改变压力反射介导的急性 AP 变化期间的尿输出功能尚不清楚。我们在接受双侧 RDN 的 SHR(n=9)中定量了 AP 与归一化尿流量(nUF)之间的关系,并将结果与假手术 SHR(n=9)进行了比较。此外,我们还检查了血管紧张素 II 型 1 受体阻滞剂替米沙坦(2.5mg/kg)对 AP-nUF 关系的急性影响。双侧 RDN 通过缩小颈动脉窦压力反射总弧的反应范围,显著降低了 AP。在基础状态下,假手术组和 RDN 组的 nUF 与平均 AP(以 μL·min·kg·mmHg 计)之间的斜率分别为 0.076±0.045 和 0.188±0.039;替米沙坦给药后的斜率分别为 0.285±0.034 和 0.416±0.078。RDN 对 nUF 斜率的影响具有边缘显著性(P=0.059),这可能改善了 RDN 组尿输出的可控性。替米沙坦对 nUF 斜率的影响在假手术组和 RDN 组均具有显著性(P<0.001),这表明无论持续的肾交感神经活动如何,循环或局部产生的血管紧张素 II 对决定尿输出功能都有贡献。

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