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血管周围脂肪组织和内源性硫化氢在正常血压和自发性高血压大鼠离体肠系膜动脉血管活性反应中的作用。

The role of perivascular adipose tissue and endogenous hydrogen sulfide in vasoactive responses of isolated mesenteric arteries in normotensive and spontaneously hypertensive rats.

机构信息

Institute of Normal and Pathological Physiology, Center of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovak Republic.

Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University, Bratislava, Slovak Republic.

出版信息

J Physiol Pharmacol. 2019 Apr;70(2). doi: 10.26402/jpp.2019.2.13. Epub 2019 Aug 20.

Abstract

Perivascular adipose tissue (PVAT) and hydrogen sulfide (HS) play important roles in the modulation of vasoactive responses and can interfere with the ethiopathogenesis of essential hypertension. The aim of this study was to evaluate the mutual relationship between PVAT and HS (endogenously produced, exogenous) in vasoactive responses of isolated mesenteric arteries (MA) in adult normotensive (Wistar) and spontaneously hypertensive rats (SHR). In SHR, hypertension was associated with cardiac hypertrophy and increased contractility; however, there were no differences in the amount of retroperitoneal fat between strains. PVAT revealed the anti-contractile effect on vasoconstriction induced by exogenous noradrenaline in both strains, but surprisingly, this effect was stronger in SHR. Concurrently; PVAT exhibited a pro-contractile effect on contractions to endogenous noradrenaline released from arterial sympathetic nerves in SHR, but not in Wistar rats. We confirmed the anti-contractile effect of HS in both, the vascular wall and PVAT of Wistar rats because the pre-treatment with propargylglycine (PPG), an inhibitor of HS producing enzyme, significantly increased the noradrenaline-induced contraction. In SHR, HS in the vascular wall exhibited a pro-contractile effect that was eliminated by the presence of PVAT; however, the pre-treatment with PPG did not affect noradrenaline contraction farther. Nevertheless, unlike in Wistar rats, the presence of PVAT potentiated the vasorelaxant effect of exogenously applied HS in SHR. Our results confirmed that PVAT of MA and endogenously produced HS could manifest as pro-contractile or as anti-contractile. In SHR, unlike in Wistar rats, the pro-contractile effect of PVAT associated with the stimulation of perivascular nerves, and the pro-contractile effect of HS in the arterial wall could represent pathologic features. On the other hand, PVAT of SHR is endowed with compensatory vasoactive mechanisms, which include stronger anti-contractile action of an unknown factor (other than HS) and potentiation of the vasorelaxant effect of exogenous HS.

摘要

血管周围脂肪组织 (PVAT) 和硫化氢 (HS) 在调节血管活性反应中发挥重要作用,并可能干扰原发性高血压的发病机制。本研究旨在评估成年正常血压(Wistar)和自发性高血压大鼠(SHR)分离的肠系膜动脉(MA)血管活性反应中 PVAT 和 HS(内源性产生、外源性)之间的相互关系。在 SHR 中,高血压与心脏肥大和收缩力增加有关;然而,两种品系之间腹膜后脂肪量没有差异。PVAT 对两种品系的外源性去甲肾上腺素诱导的血管收缩均表现出抗收缩作用,但令人惊讶的是,这种作用在 SHR 中更强。同时,PVAT 对动脉交感神经释放的内源性去甲肾上腺素引起的收缩表现出促收缩作用,但在 Wistar 大鼠中没有。我们证实了 HS 在 Wistar 大鼠血管壁和 PVAT 中的抗收缩作用,因为 HS 产生酶抑制剂炔丙基甘氨酸(PPG)的预处理显著增加了去甲肾上腺素引起的收缩。在 SHR 中,血管壁中的 HS 表现出促收缩作用,而 PVAT 的存在则消除了这种作用;然而,PPG 的预处理进一步不影响去甲肾上腺素的收缩。然而,与 Wistar 大鼠不同的是,PVAT 的存在增强了 SHR 中外源性 HS 的血管舒张作用。我们的结果证实,MA 的 PVAT 和内源性产生的 HS 可能表现出促收缩或抗收缩作用。在 SHR 中,与刺激血管周围神经相关的 PVAT 的促收缩作用,以及 HS 在动脉壁中的促收缩作用,可能代表病理特征。另一方面,SHR 的 PVAT 具有代偿性的血管活性机制,包括未知因素(除 HS 之外)的更强的抗收缩作用以及外源性 HS 的血管舒张作用的增强。

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