血管活性物质对雌雄达尔盐敏感大鼠阻力小动脉生物力学的影响

IF 2.9 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pharmacology Research & Perspectives Pub Date : 2024-04-01 DOI:10.1002/prp2.1180
Eric A Mensah, Noriko Daneshtalab, Reza Tabrizchi
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摘要

血管生物力学的变化导致动脉僵化增加,在循环功能障碍中起着关键作用。我们的目的是研究与生物力学相关的性别特异性药理学变化以及对达尔盐敏感的雌雄大鼠阻力小动脉的结构改变。利用压力肌电图记录测定了复合杨氏模量(CYM),并使用免疫组织化学方法评估了三阶肠系膜动脉(n = 6)的任何结构变化。与普通饮食动物相比,高盐饮食动物患高血压,中心血压和外周血压以及脉搏波速度显著升高。在车辆处理的时间对照研究中,没有观察到任何组别(即雄性和雌性)之间的 CYM 存在明显差异。与车辆相比,维拉帕米(0.3 μM)能显著降低高血压男性的 CYM,而女性则没有变化。苯肾上腺素(0.3 μM)可消除这种效应。与载体相比,BaCl2(100 μM)、uabain(100 μM)和 L-NAME(0.3 μM)合用可明显增加正常血压男性和女性血管中的 CYM,但对高血压男性没有影响。在苯肾上腺素存在的情况下,CYM 的增加被取消。在苯肾上腺素存在的情况下,硝普钠(0.3 μM)可显著降低正常血压男性与高血压男性的 CYM,但女性之间没有差异。在对动脉僵化的生物力学标志物进行免疫组化评估时,观察到男性和女性之间存在明显差异。我们的研究结果表明,压力差异可能是造成生物力学适应性变化以及高血压状态下不同药理反应的原因。
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Effects of vasoactive substances on biomechanics of small resistance arteries of male and female Dahl salt-sensitive rats.

Changes in vascular biomechanics leading to increase in arterial stiffness play a pivotal role in circulatory dysfunction. Our objectives were to examine sex-specific pharmacological changes related to the biomechanics and any structural modifications in small resistance arteries of Dahl salt-sensitive male and female rats. The composite Young modulus (CYM) was determined using pressure myograph recordings, and immunohistochemistry was used for the evaluation of any structural changes in the third-order mesenteric arteries (n = 6). Animals on high-salt diet developed hypertension with significant elevation in central and peripheral blood pressures and pulse wave velocity compared to those on regular diet. There were no significant differences observed in the CYM between any of the groups (i.e., males and females) in vehicle-treated time-control studies. The presence of verapamil (0.3 μM) significantly reduced CYM in hypertensive males without changes within females compared to vehicle. This effect was abolished by phenylephrine (0.3 μM). BaCl2 (100 μM), ouabain (100 μM), and L-NAME (0.3 μM) combined significantly increased CYM in vessels from in normotensive males and females but not in hypertensive males compared to vehicle. The increase in CYM was abolished in the presence of phenylephrine. Sodium nitroprusside (0.3 μM), in the presence of phenylephrine, significantly reduced CYM in male normotensive versus hypertensive, with no differences within females. Significant differences were observed in immunohistochemical assessment of biomechanical markers of arterial stiffness between males and females. Our findings suggest sex possibly due to pressure differences to be responsible for adaptive changes in biomechanics, and varied pharmacological responses in hypertensive state.

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来源期刊
Pharmacology Research & Perspectives
Pharmacology Research & Perspectives Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics
CiteScore
5.30
自引率
3.80%
发文量
120
审稿时长
20 weeks
期刊介绍: PR&P is jointly published by the American Society for Pharmacology and Experimental Therapeutics (ASPET), the British Pharmacological Society (BPS), and Wiley. PR&P is a bi-monthly open access journal that publishes a range of article types, including: target validation (preclinical papers that show a hypothesis is incorrect or papers on drugs that have failed in early clinical development); drug discovery reviews (strategy, hypotheses, and data resulting in a successful therapeutic drug); frontiers in translational medicine (drug and target validation for an unmet therapeutic need); pharmacological hypotheses (reviews that are oriented to inform a novel hypothesis); and replication studies (work that refutes key findings [failed replication] and work that validates key findings). PR&P publishes papers submitted directly to the journal and those referred from the journals of ASPET and the BPS
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