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Cogolludo AL, Moral-Sanz J, van der Sterren S, Frazziano G, van Cleef AN, Menendez C, Zoer B, Moreno E, Roman A, Perez-Vizcaino F, Villamor E: Maturation of O2 sensing and signaling in the chicken ductus arteriosus. . Am J Physiol Lung Cell Mol Physiol. 2009 Oct;297(4):L619-30. Epub 2009 Jul 17.
The increase in O (2) tension after birth is a major factor stimulating ductus arteriosus (DA) constriction and closure. Here we studied the role of the mitochondrial electron transport chain (ETC) as sensor, H (2) O (2) as mediator, and voltage-gated potassium (K (V)) channels and Rho kinase as effectors of O (2)-induced contraction in the chicken DA during fetal development. Switching from 0% to 21% O (2) contracted the pulmonary side of the mature DA (mature pDA) but had no effect in immature pDA and relaxed the aortic side of the mature DA (mature aDA). This contraction of the pDA was attenuated by inhibitors of the mitochondrial ETC and by the H (2) O (2) scavenger polyethylene glycol (PEG)-catalase. Moreover, O (2) increased reactive oxygen species (ROS) production, measured with the fluorescent probes dihydroethidium and 2',7'-dichlorofluorescein, only in mature pDA. The H (2) O (2) analog t-butyl-hydroperoxide mimicked the responses to O (2) in the three vessels. In contrast to immature pDA cells, mature pDA cells exhibited high-amplitude O (2)-sensitive potassium currents. The K (V) channel blocker 4-aminopyridine prevented the current inhibition elicited by O (2). The L-type Ca (2+) (Ca (L)) channel blocker nifedipine and the Rho kinase inhibitors Y-27632 and hydroxyfasudil induced a similar relaxation when mature pDA were stimulated with O (2) or H (2) O (2). Moreover, the sensitivity to these drugs increased with maturation. Our results indicate the presence of a common mechanism for O (2) sensing/signaling in mammalian and nonmammalian DA and favor the idea that, rather than a single mechanism, a parallel maturation of the sensor and effectors is critical for O (2) sensitivity appearance during development. |
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