Department of Physiology, School of Medicine, College of Medicine and Health, University College Cork, Cork, Ireland.
Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
J Hypertens. 2024 Jun 1;42(6):1027-1038. doi: 10.1097/HJH.0000000000003689. Epub 2024 Feb 28.
Reno-renal reflexes are disturbed in cardiovascular and hypertensive conditions when elevated levels of pro-inflammatory mediators/cytokines are present within the kidney. We hypothesised that exogenously administered inflammatory cytokines tumour necrosis factor alpha (TNF-α) and interleukin (IL)-1β modulate the renal sympatho-excitatory response to chemical stimulation of renal pelvic sensory nerves.
In anaesthetised rats, intrarenal pelvic infusions of vehicle [0.9% sodium chloride (NaCl)], TNF-α (500 and 1000 ng/kg) and IL-1β (1000 ng/kg) were maintained for 30 min before chemical activation of renal pelvic sensory receptors was performed using randomized intrarenal pelvic infusions of hypertonic NaCl, potassium chloride (KCl), bradykinin, adenosine and capsaicin.
The increase in renal sympathetic nerve activity (RSNA) in response to intrarenal pelvic hypertonic NaCl was enhanced during intrapelvic TNF-α (1000 ng/kg) and IL-1β infusions by almost 800% above vehicle with minimal changes in mean arterial pressure (MAP) and heart rate (HR). Similarly, the RSNA response to intrarenal pelvic adenosine in the presence of TNF-α (500 ng/kg), but not IL-1β, was almost 200% above vehicle but neither MAP nor HR were changed. There was a blunted sympatho-excitatory response to intrapelvic bradykinin in the presence of TNF-α (1000 ng/kg), but not IL-1β, by almost 80% below vehicle, again without effect on either MAP or HR.
The renal sympatho-excitatory response to renal pelvic chemoreceptor stimulation is modulated by exogenous TNF-α and IL-1β. This suggests that inflammatory mediators within the kidney can play a significant role in modulating the renal afferent nerve-mediated sympatho-excitatory response.
当肾脏内存在升高水平的促炎介质/细胞因子时，肾-肾反射在心血管和高血压疾病中会受到干扰。我们假设，外源性给予炎性细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）会调节肾交感神经兴奋对肾盂感觉神经化学刺激的反应。
在麻醉大鼠中，在 30 分钟内持续进行肾盂内输注载体[0.9%氯化钠（NaCl）]、TNF-α（500 和 1000ng/kg）和 IL-1β（1000ng/kg），然后使用随机的肾盂内高渗 NaCl、氯化钾（KCl）、缓激肽、腺苷和辣椒素输注来化学激活肾盂感觉受体。
与载体相比，TNF-α（1000ng/kg）和 IL-1β 存在时，肾盂内高渗 NaCl 引起的肾交感神经活动（RSNA）增加了近 800%，而平均动脉压（MAP）和心率（HR）仅略有变化。同样，TNF-α（500ng/kg）存在时，肾盂内腺苷引起的 RSNA 反应比载体增加了近 200%，但 MAP 和 HR 均未改变。TNF-α（1000ng/kg）存在时，肾盂内缓激肽引起的交感神经兴奋反应减弱了近 80%，但 MAP 和 HR 均未改变。
肾化学感受器刺激引起的肾交感神经兴奋反应受到外源性 TNF-α和 IL-1β的调节。这表明肾脏内的炎症介质可以在调节肾传入神经介导的交感神经兴奋反应中发挥重要作用。
