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猪健康妊娠后冠状动脉反应性的功能适应性

Functional Adaptations in Coronary Reactivity following Healthy Pregnancy in Swine.

作者信息

Tucker Selina M, Essajee Salman I, Warne Cooper M, Dick Gregory M, Goulopoulou Styliani, Tune Johnathan D

机构信息

Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, Texas, USA.

MD Center for Perinatal Biology, Departments of Basic Sciences, Gynecology and Obstetrics, Loma Linda University, Loma Linda, California, USA.

出版信息

J Vasc Res. 2025;62(2):78-87. doi: 10.1159/000543116. Epub 2024 Dec 11.

Abstract

INTRODUCTION

This study was designed to test the hypothesis that coronary artery adaptations during the postpartum period are related to underlying reductions in endothelium-dependent relaxation and/or augmented smooth muscle vasoconstrictor responsiveness.

METHODS

In vivo experiments were performed in control (nonpregnant) and postpartum swine 35-45 days of postdelivery, with isometric tension experiments performed in isolated coronary arteries from those animals.

RESULTS

Coronary artery rings demonstrated increases in active tension generation following incremental increases in passive stretch with no differences between groups. Endothelium-dependent relaxation to bradykinin was attenuated in arteries from postpartum swine versus control (p < 0.005). Concentration-dependent contractions to the thromboxane A2 mimetic U46619 (0.1 nm-1 µm) were shifted rightward (EC50 27 ± 10 nm vs. 238 ± 66 nm; p < 0.01) in arteries from postpartum swine, with no changes in maximum contractile responses (p = 0.68). Intracoronary administration of U46619 (1 nm-1 µm) in open-chest swine decreased coronary blood flow ∼45 ± 3% in nonpregnant controls but had no effect on coronary blood flow in postpartum swine. Concentration-dependent contractions to KCl (5-90 mm) showed a rightward shift in arteries from postpartum swine (15.6 ± 1.4 mm vs. 21.8 ± 1.9 mm; p = 0.03), with no change in maximum response. Taken together, the postpartum period is associated with reduced endothelium-dependent relaxation and responsiveness to receptor-dependent and -independent vasoconstrictor stimuli.

CONCLUSION

These findings indicate that chronic exposure of the coronary circulation to the pregnancy/postpartum milieu results in functional adaptations in sensitivity to paracrine/hormonal compounds that should be further explored.

摘要

引言

本研究旨在验证以下假设,即产后冠状动脉的适应性变化与内皮依赖性舒张功能的潜在降低和/或平滑肌血管收缩反应性增强有关。

方法

对分娩后35 - 45天的对照(未怀孕)母猪和产后母猪进行体内实验,并对这些动物的离体冠状动脉进行等长张力实验。

结果

随着被动拉伸的逐渐增加,冠状动脉环的主动张力产生增加,两组之间无差异。与对照组相比,产后母猪动脉对缓激肽的内皮依赖性舒张功能减弱(p < 0.005)。产后母猪动脉对血栓素A2模拟物U46619(0.1 nM - 1 μM)的浓度依赖性收缩反应向右移位(半数有效浓度[EC50]:27±10 nM对238±66 nM;p < 0.01),最大收缩反应无变化(p = 0.68)。在开胸猪体内冠状动脉内注射U46619(1 nM - 1 μM),未怀孕对照组的冠状动脉血流量减少约45±3%,但对产后母猪的冠状动脉血流量无影响。产后母猪动脉对氯化钾(5 - 90 mM)的浓度依赖性收缩反应向右移位(15.6±1.4 mM对21.8±1.9 mM;p = 0.03),最大反应无变化。综上所述,产后时期与内皮依赖性舒张功能降低以及对受体依赖性和非依赖性血管收缩刺激的反应性降低有关。

结论

这些发现表明,冠状动脉循环长期暴露于妊娠/产后环境会导致对旁分泌/激素化合物敏感性的功能适应性变化,这一点值得进一步研究。

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