高血压大鼠血管收缩和舒张介质的昼夜节律变化及压力反射敏感性

Q2 Biochemistry, Genetics and Molecular Biology

Journal of Circadian Rhythms Pub Date : 2019-10-14 DOI:10.5334/jcr.185

T. Kezeli, N. Gongadze, G. Sukoyan, Marina Shikhashvili, Z. Chapichadze, M. Okujava, N. Dolidze

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引用次数: 2

摘要

本研究的目的是评估血管舒张物质降钙素基因相关肽（CGRP）和环氧二十碳三烯酸（EETs）和血管收缩剂内皮素-1（ET1）的昼夜节律与动脉高压模型Wistar大鼠心脏血液动力学指数（CHI）和压力反射（BRS）的日节律之间的关系（1K-1C-AH）。将动物分为3组：I-假手术（SO）组、II-4周组和III-8周组。每4小时研究一次ET1、CGRP和EET的血浆浓度。在有意识自由运动的1K-1C AH大鼠中，与SO动物不同，血压（BP）、心搏周期（HP）和BRS经历了显著的昼夜节律波动，与4周高血压大鼠相比，8周高血压大白鼠的血压平均值更显著增加（179±5 vs.162±4 mm Hg，p<0.05）。这些变化与8周1K-1C AH大鼠的HP（138±5 vs.150±6 ms，p<0.05）和BRS（0.44±0.04 vs.0.58±0.04 ms mm Hg-1，p<0.05）的更显著降低相关。与4周相比，8周1K-1C AH大鼠的BP峰相转移到更多的深夜时间（凌晨1点58分对晚上11点32分），并且在两组动物中，CGRP和EET的昼夜节律血浆水平最低，ET1水平最高。与持续4周的1K-1C AH大鼠相比，SO大鼠的BP值较低（121±3 mm Hg，p＜0.05），HP指数较高（158±2 ms，p＜0.01）和BRS指数较高（0.86±0.02 ms mmHg–1，p＜0001）。高血压动物的BP、HP和BRS在14.8±0.5h、13.6±0.4h和13.1±0.2h出现顶相，这与ET1和CGRP在24:00和EETs在12:00的最大昼夜节律含量相关，并且与假手术组相比发生了变化。在患有1K-1C AH的大鼠中，血浆ET1、CGRP和EET水平经历昼夜节律波动，CHI和BRS发生相应变化，在疾病晚期更显著地表达，可用于未来动脉高血压的预测、预防和个性化治疗。

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Circadian Variation in Vasoconstriction and Vasodilation Mediators and Baroreflex Sensitivity in Hypertensive Rats

The purpose of this study was to evaluate the relationship between the circadian profile of the vasorelaxing substances calcitonin gene-related peptide (CGRP) and epoxyeicosatrienoic acids (EETs) and the vasconstrictive agent endothelin-1 (ET1) and the daily rhythms of cardiac hemodynamic indices (CHI) and baroreflex (BRS) in Wistar rats with 1 kidney-1 clip model of arterial hypertension (1K-1C AH). The animals were divided into 3 groups: I- sham-operated (SO), II- 4-week and III- 8-week 1K-1C AH rats. Plasma concentration of ET1, CGRP and EET’s were investigated every 4 h. In conscious freely moving 1K-1C AH rats unlike SO animals blood pressure (BP), heart period (HP) and BRS underwent significant circadian fluctuations, with more marked increase in mean values of BP in 8-week hypertensive rats in comparison to 4-week hypertensive rats (179 ± 5 vs. 162 ± 4 mm Hg, p < 0.05). These alterations correlated with more significant reduction in HP (138 ± 5 vs. 150 ± 6 ms, p < 0,05) and BRS (0.44 ± 0.04 vs. 0.58 ± 0.04 ms mm Hg–1, p < 0.05) in 8-week 1K-1C AH rats. The acrophases of BP in 8-week 1K-1C AH rats in comparison with 4-week were shifted to more late night hours (1:58 a.m. vs. 11:32 p.m.) and in both groups of animals corresponded to lowest circadian plasma levels of CGRP and EETs and to greatest level of ET1. SO rats were characterized by lower values of BP (121 ± 3 mm Hg, p < 0,05) and higher indices of HP (158 ± 2 ms, p < 0,05) and BRS (0.86 ± 0.02 ms mmHg–1, p < 0,001) in comparison with 1K-1C AH rats 4-week duration. The acrophases of BP, HP and BRS in hypertensive animals were revealed at 14.8 ± 0.5 h, 13.6 ± 0.4 h and 13.1 ± 0.2 h, which correlated with maximal circadian contents of ET1 and CGRP at 24:00 h and EETs at 12:00 h and were shifted in comparison to sham-operated group. In rats with 1K-1C AH, plasma levels of ET1, CGRP and EETs undergo circadian fluctuation with corresponding alterations in CHI and BRS which are more markedly expressed on the late stage of diseases and could be used in future for predictive, preventive, and personalized treatment of arterial hypertension.

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来源期刊

Journal of Circadian Rhythms Biochemistry, Genetics and Molecular Biology-Physiology

CiteScore

7.10

自引率

0.00%

发文量

审稿时长

12 weeks

期刊介绍： Journal of Circadian Rhythms is an Open Access, peer-reviewed online journal that publishes research articles dealing with circadian and nycthemeral (daily) rhythms in living organisms, including processes associated with photoperiodism and daily torpor. Journal of Circadian Rhythms aims to include both basic and applied research at any level of biological organization (molecular, cellular, organic, organismal, and populational). Studies of daily rhythms in environmental factors that directly affect circadian rhythms are also pertinent to the journal"s mission.