Journal of vascular research · 2024
Functional Adaptations in Coronary Reactivity following Healthy Pregnancy in Swine.
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Tucker Selina M, Essajee Salman I, Warne Cooper M, Dick Gregory M, Goulopoulou Styliani, Tune Johnathan D
Аннотация
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 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.
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.
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 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.
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.