Functional Adaptations in Coronary Reactivity following Healthy Pregnancy in Swine

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.