School of Life Sciences, University of Nottingham, Nottingham, UK.
Acta Physiol (Oxf). 2018 Dec;224(4):e13126. doi: 10.1111/apha.13126. Epub 2018 Jul 11.
Hypoxia causes vasodilatation of coronary arteries which protects the heart from ischaemic damage through mechanisms including the generation of hydrogen sulphide (H S), but the influence of the perivascular adipose tissue (PVAT) and myocardium is incompletely understood. This study aimed to determine whether PVAT and the myocardium modulate the coronary artery hypoxic response and whether this involves hydrogen sulphide.
Porcine left circumflex coronary arteries were prepared as cleaned segments and with PVAT intact, myocardium intact or both PVAT and myocardium intact, and contractility investigated using isometric tension recording. Immunoblotting was used to measure levels of H S-synthesizing enzymes: cystathionine-β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulphurtransferase (MPST).
All three H S-synthesizing enzymes were detected in the artery and myocardium, but only CBS and MPST were detected in PVAT. Hypoxia elicited a biphasic response in cleaned artery segments consisting of transient contraction followed by prolonged relaxation. In arteries with PVAT intact, hypoxic contraction was attenuated and relaxation augmented. In arteries with myocardium intact, hypoxic contraction was attenuated, but relaxation was unaffected. In replacement experiments, replacement of dissected PVAT and myocardium attenuated artery contraction and augmented relaxation to hypoxia, mimicking the effect of in situ PVAT and indicating involvement of a diffusible factor(s). In arteries with intact PVAT, augmentation of hypoxic relaxation was reversed by amino-oxyacetate (CBS inhibitor), but not DL-propargylglycine (CSE inhibitor) or aspartate (inhibits MPST pathway).
PVAT augments hypoxic relaxation of coronary arteries through a mechanism involving H S and CBS, pointing to an important role in regulation of coronary blood flow during hypoxia.
缺氧引起冠状动脉扩张，通过生成硫化氢（H₂S）等机制保护心脏免受缺血损伤，但血管周围脂肪组织（PVAT）和心肌的影响尚不完全清楚。本研究旨在确定 PVAT 和心肌是否调节冠状动脉缺氧反应，以及这是否涉及硫化氢。
将猪左回旋支冠状动脉制备为清洁段，保留 PVAT、心肌完整或同时保留 PVAT 和心肌完整，并使用等长张力记录法研究收缩性。免疫印迹法用于测量 H₂S 合成酶的水平：胱硫醚-β-合酶（CBS）、胱硫醚 γ-裂合酶（CSE）和 3-巯基丙酮酸硫转移酶（MPST）。
所有三种 H₂S 合成酶在动脉和心肌中均有检测到，但仅在 PVAT 中检测到 CBS 和 MPST。缺氧在清洁的动脉段引起双相反应，包括短暂收缩后长时间舒张。在保留 PVAT 的动脉中，缺氧收缩减弱，舒张增强。在保留心肌的动脉中，缺氧收缩减弱，但舒张不受影响。在替换实验中，分离的 PVAT 和心肌的替换减弱了动脉对缺氧的收缩，增强了对缺氧的舒张，模拟了原位 PVAT 的作用，并表明涉及可扩散因子（s）。在保留完整 PVAT 的动脉中，CBS 抑制剂氨基氧乙酸（amino-oxyacetate）逆转了缺氧舒张的增强，但 CSE 抑制剂 DL-丙炔基甘氨酸（DL-propargylglycine）或天冬氨酸（inhibits MPST pathway）没有。
PVAT 通过涉及 H₂S 和 CBS 的机制增强冠状动脉的缺氧舒张，这表明其在缺氧期间调节冠状动脉血流中起着重要作用。
