Selina M Tucker, Salman I Essajee, Cooper M Warne, Gregory M Dick, Styliani Goulopoulou, Johnathan D Tune
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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 n<sc>m</sc>-1 µ<sc>m</sc>) were shifted rightward (EC50 27 ± 10 n<sc>m</sc> vs. 238 ± 66 n<sc>m</sc>; p < 0.01) in arteries from postpartum swine, with no changes in maximum contractile responses (p = 0.68). Intracoronary administration of U46619 (1 n<sc>m</sc>-1 µ<sc>m</sc>) 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 m<sc>m</sc>) showed a rightward shift in arteries from postpartum swine (15.6 ± 1.4 m<sc>m</sc> vs. 21.8 ± 1.9 m<sc>m</sc>; 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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"1-10"},"PeriodicalIF":1.8000,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Functional Adaptations in Coronary Reactivity following Healthy Pregnancy in Swine.\",\"authors\":\"Selina M Tucker, Salman I Essajee, Cooper M Warne, Gregory M Dick, Styliani Goulopoulou, Johnathan D Tune\",\"doi\":\"10.1159/000543116\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 n<sc>m</sc>-1 µ<sc>m</sc>) were shifted rightward (EC50 27 ± 10 n<sc>m</sc> vs. 238 ± 66 n<sc>m</sc>; p < 0.01) in arteries from postpartum swine, with no changes in maximum contractile responses (p = 0.68). Intracoronary administration of U46619 (1 n<sc>m</sc>-1 µ<sc>m</sc>) 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 m<sc>m</sc>) showed a rightward shift in arteries from postpartum swine (15.6 ± 1.4 m<sc>m</sc> vs. 21.8 ± 1.9 m<sc>m</sc>; p = 0.03), with no change in maximum response. 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引用次数: 0
摘要
本研究验证了产后冠状动脉适应与内皮依赖性松弛和/或平滑肌血管收缩反应增强的潜在减少有关的假设。体内实验在分娩后35-45天的对照组(未怀孕)和产后猪中进行,并在这些动物的分离冠状动脉中进行等长张力实验。随着被动拉伸的增加,冠状动脉环的主动张力增加,两组间无差异。与对照组相比,产后仔猪对缓激肽的内皮依赖性松弛减弱(P < 0.005)。血栓素A2模拟物U46619的收缩(0.1 nM - 1µM)右移(EC50 27±10 nM vs. 238±66 nM;P < 0.01),最大反应无变化(P = 0.68)。在开胸猪冠状动脉内注射U46619 (1 nM - 1µM)可使未怀孕猪冠状动脉血流减少~45±3%,但对产后猪冠状动脉血流无影响。产后猪动脉向KCl (5 - 90mm)的收缩显示右移(15.6±1.4 mM vs. 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松弛和对受体依赖性和独立血管收缩刺激的反应性降低有关。
Functional Adaptations in Coronary Reactivity following Healthy Pregnancy in Swine.
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.
期刊介绍:
The ''Journal of Vascular Research'' publishes original articles and reviews of scientific excellence in vascular and microvascular biology, physiology and pathophysiology. The scope of the journal covers a broad spectrum of vascular and lymphatic research, including vascular structure, vascular function, haemodynamics, mechanics, cell signalling, intercellular communication, growth and differentiation. JVR''s ''Vascular Update'' series regularly presents state-of-the-art reviews on hot topics in vascular biology. Manuscript processing times are, consistent with stringent review, kept as short as possible due to electronic submission. All articles are published online first, ensuring rapid publication. The ''Journal of Vascular Research'' is the official journal of the European Society for Microcirculation. A biennial prize is awarded to the authors of the best paper published in the journal over the previous two years, thus encouraging young scientists working in the exciting field of vascular biology to publish their findings.