年龄和高血压相关变化对大鼠胸主动脉中 NOS/NO/sGC 衍生血管活性控制的影响。

Age- and Hypertension-Related Changes in NOS/NO/sGC-Derived Vasoactive Control of Rat Thoracic Aortae.

机构信息

Institute of Normal and Pathological Physiology, Centre of Experimental Medicine Slovak Academy of Sciences, Bratislava 84104, Slovakia.

出版信息

Oxid Med Cell Longev. 2022 Mar 9;2022:7742509. doi: 10.1155/2022/7742509. eCollection 2022.

DOI:10.1155/2022/7742509

PMID:35308173

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8926472/

Abstract

This study was aimed at examining the role of the NOS/NO/sGC signaling pathway in the vasoactive control of the thoracic aorta (TA) from the early to late ontogenetic stages (7 weeks, 20 weeks, and 52 weeks old) of normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Systolic blood pressure (SBP) and heart rate (HR) were significantly increased in SHRs compared to age-matched WKYs, which was associated with left heart ventricle hypertrophy in all age groups of rats. The plasma urea level was increased in 20-week-old and 52-week-old SHRs compared with WKYs without increasing creatinine and uric acid. The total cholesterol levels were lower in 20-week-old and 52-week-old SHRs than in WKYs, but triglycerides were higher in 7-week-old SHRs. The fructosamine level was increased in 52-week-old SHRs compared with age-matched WKYs and unchanged in other age groups. Superoxide production was increased only in 7-week-old SHRs compared to age-matched WKYs. The endothelium-dependent relaxation (EDR) of the TA deteriorated in both rat strains during aging; however, endothelial dysfunction already occurred in 20-week-old SHRs and was even more enhanced in 52-week-old rats. Our results also demonstrated increased activity of NOS in 52-week-old WKYs. Moreover, 7-week-old and 52-week-old WKY rats displayed an enhanced residual EDR after L-NMMA (NOS inhibitor) incubation compared with 20-week-old rats. Our results showed that in 7-week-old SHRs, the residual EDR after L-NMMA incubation was increased compared to that in other age groups. The activity of NOS in the TA was comparable in 7-week-old and 20-week-old SHRs, but it was reduced in 52-week-old SHRs compared to younger SHRs and 52-week-old WKYs. Thus, it seems that, in contrast to SHRs, the NOS/NO system in WKYs is probably able to respond to age-related pathologies to maintain endothelial functions and thus optimal BP levels even in later periods of life.

摘要

本研究旨在探讨 NOS/NO/sGC 信号通路在正常血压的 Wistar-Kyoto（WKY）大鼠和自发性高血压大鼠（SHR）从早期到晚期胚胎发育阶段（7 周、20 周和 52 周龄）的胸主动脉（TA）血管活性控制中的作用。与同龄的 WKY 相比，SHR 的收缩压（SBP）和心率（HR）显著升高，所有年龄段的大鼠均伴有左心室肥厚。与 WKY 相比，20 周龄和 52 周龄的 SHR 血浆尿素水平升高，但肌酐和尿酸没有升高。20 周龄和 52 周龄的 SHR 总胆固醇水平低于 WKY，但 7 周龄的 SHR 甘油三酯水平较高。与同龄的 WKY 相比，52 周龄的 SHR 果糖胺水平升高，而其他年龄组则不变。与同龄的 WKY 相比，只有 7 周龄的 SHR 超氧化物产量增加。随着年龄的增长，两种大鼠的 TA 内皮依赖性舒张（EDR）均恶化；然而，内皮功能障碍在 20 周龄的 SHR 中已经发生，并且在 52 周龄的大鼠中更为明显。我们的结果还表明，52 周龄的 WKY 中 NOS 的活性增加。此外，与 20 周龄的大鼠相比，7 周龄和 52 周龄的 WKY 大鼠在 L-NMMA（NOS 抑制剂）孵育后，残留的 EDR 活性增加。我们的结果表明，与其他年龄组相比，7 周龄 SHR 孵育后 L-NMMA 的残留 EDR 增加。7 周龄和 20 周龄 SHR 的 TA 中 NOS 活性相当，但与年轻的 SHR 和 52 周龄的 WKY 相比，52 周龄的 SHR 活性降低。因此，与 SHR 相反，WKY 中的 NOS/NO 系统可能能够对与年龄相关的病理反应，以维持内皮功能，从而维持最佳的血压水平，即使在生命的后期。