Influence of excessive salt consumption on the functional state of microvascular vessels of the skin of rats with renal dysfunction

G. Ivanova, M. Khasun, M. Parastaeva, A. S. Rumyantsev, O. Beresneva
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Abstract

Background. Cardiovascular complications are common in chronic kidney disease (CKD). The relationship between the cardiovascular system and the kidneys is complex and diverse, but the question of the mechanisms of the influence of excess NaCl consumption on the functional state of blood vessels during renal dysfunction remains relevant.The aim: to evaluate the effect of a high-salt diet on the functional state of microcirculatory vessels (MCR) of the skin in rats at an early stage of renal dysfunction.Material and Methods. The study was conducted on Wistar rats. The first SO group included animals subjected to sham surgery (SO) and receiving a standard diet (0.34% NaCl); in the second, HS group – animals that also underwent a sham operation, but received a high-salt diet (4% NaCl); in the third, NE group – rats subjected to ¾ nephrectomy (NE) and receiving a standard diet; the fourth, HS+ NE group included rats subjected to ¾ NE and fed a high-salt diet (4% NaCl). Blood pressure (BP) was measured in the tail using the cuff method (Sistola, Russia), MCR was assessed using laser Doppler flowmetry (LDF). The reactivity of skin microvessels was assessed by changes in the MCR index before and after iontophoresis of acetylcholine (ACh) and sodium nitroprusside (NP). Based on the assessment of the spectral characteristics of fluctuations in the MCR index obtained using Wavelet analysis, the value of endothelial, neurogenic and myogenic microvascular tone was calculated.Results. 4 months after ¾ NE, rats showed a decrease in the excretory function of the kidneys. In rats on a highsalt diet, an increase in blood urea levels was noted. The blood pressure in rats of the SO+HS group did not significantly differ from the control animals of the SO group (131 ± 8 and 125 ± 4 mmHg, respectively, NS), NE led to a significant increase in blood pressure (135 ± 5 mmHg in rats of the NE group, and 145 ± 7 mmHg – in the NE+HS group). The average MCR was higher in rats receiving a high-salt diet (SO+HS and NE+HS groups), compared with animals of the corresponding group receiving a standard diet. The combination of NE and high-salt load has an inhibitory effect on the amplitude of fluctuations in the intensity of perfusion in all studied ranges: endothelial, neurogenic and myogenic, while the calculated value of skin microvascular tone in three ranges was the highest in NE+HS group rats. In all experimental groups, the reactivity to AH was reduced compared with the SO group, and after NP iontophoresis, the average perfusion rate significantly decreased only in groups of animals receiving a high-salt diet: SO+HS and NE+HS.Conclusion. A high-salt diet in rats with an initial stage of renal dysfunction contributes to an increase in blood pressure and a decrease in natriuresis compared with animals with NE who received a standard diet. With excessive consumption of table salt in rats after NE, the intensity of cutaneous MCR increases, while reducing the variability of the MCR index. A high-salt diet in rats with NE modifies the characteristics of the spectral components of fluctuations in the MCR index, indicating an increase in tonic effects on skin microvessels in the endothelial, neurogenic and myogenic ranges. With hypernatrial load, animals with ¾ NE have a decrease in the reactivity of cutaneous microvessels to AH and NP, which is mediated by both a decrease in endothelial NO production and a decrease in MMC sensitivity to NO.
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过量食盐对肾功能不全大鼠皮肤微血管功能状态的影响
背景。心血管并发症是慢性肾脏病(CKD)的常见病。心血管系统与肾脏之间的关系复杂多样,但肾功能不全期间过量摄入 NaCl 对血管功能状态的影响机制问题仍具有现实意义。研究目的:评估高盐饮食对肾功能不全早期大鼠皮肤微循环血管(MCR)功能状态的影响。研究对象为 Wistar 大鼠。第一组为SO组,包括接受假手术(SO)并摄入标准饮食(0.34% NaCl)的动物;第二组为HS组,包括同样接受假手术但摄入高盐饮食(4% NaCl)的动物;第三组为NE组,包括接受3/4肾切除术(NE)并摄入标准饮食的大鼠;第四组为HS+ NE组,包括接受3/4 NE并摄入高盐饮食(4% NaCl)的大鼠。使用袖带法(Sistola,俄罗斯)测量尾部血压(BP),使用激光多普勒血流测量仪(LDF)评估MCR。通过乙酰胆碱(ACh)和硝普钠(NP)离子透入前后的 MCR 指数变化评估皮肤微血管的反应性。根据小波分析获得的 MCR 指数波动频谱特征评估,计算出内皮、神经和肌源性微血管张力值。4 个月后,大鼠的肾脏排泄功能下降。高盐饮食大鼠的血尿素水平升高。SO+HS 组大鼠的血压与 SO 组对照组大鼠的血压无明显差异(分别为 131 ± 8 mmHg 和 125 ± 4 mmHg,NS),而 NE 会导致血压显著升高(NE 组大鼠的血压为 135 ± 5 mmHg,NE+HS 组大鼠的血压为 145 ± 7 mmHg)。与接受标准饮食的相应组别动物相比,接受高盐饮食的大鼠(SO+HS 组和 NE+HS 组)的平均 MCR 值更高。NE 和高盐负荷的组合对所有研究范围内的灌注强度波动幅度都有抑制作用:内皮、神经源和肌源性,而 NE+HS 组大鼠在三个范围内的皮肤微血管张力计算值最高。与 SO 组相比,所有实验组的大鼠对 AH 的反应性都有所降低:结论。结论:与接受标准饮食的 NE 动物相比,肾功能不全初期大鼠的高盐饮食会导致血压升高和尿量减少。NE 后的大鼠过量食用食盐会增加皮肤 MCR 的强度,同时降低 MCR 指数的变异性。NE 大鼠的高盐饮食会改变 MCR 指数波动的频谱成分特征,这表明在内皮、神经源和肌源性范围内,对皮肤微血管的强直作用会增加。在高心房负荷的情况下,NE 含量为 3/4 的动物皮肤微血管对 AH 和 NP 的反应性降低,其原因是内皮 NO 生成减少和 MMC 对 NO 的敏感性降低。
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