| Autor: |
Cogolludo, Angel L., Moral-Sanz, Javier, van der Sterren, Saskia, Frazziano, Giovanna, van Cleef, Anne N. H., Menéndez, Carmen, Zoer, Bea, Moreno, Enrique, Roman, Angela, Pérez-Vizcaino, Francisco, Villamor, Eduardo |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Lung Cellular & Molecular Physiology; Oct2009, Vol. 297, pL619-L630, 12p |
| Abstrakt: |
The increase in O2 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, H2O2 as mediator, and voltage-gated potassium (Ky) channels and Rho kinase as effectors of O2-induced contraction in the chicken DA during fetal development. Switching from 0% to 21% O2 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 H2O2 scavenger polyethylene glycol (PEG)-catalase. Moreover, O2 increased reactive oxygen species (ROS) production, measured with the fluorescent probes dihydroethidium and 2',7'-dichlorofluorescein, only in mature pDA. The H2O2 analog t-butyl-hydroperoxide mimicked the responses to O2 in the three vessels. In contrast to immature pDA cells, mature pDA cells exhibited high-amplitude O2-sensitive potassium currents. The Kv channel blocker 4-aminopyridine prevented the current inhibition elicited by O2. The L-type Ca2+ (CaL) channel blocker nifedipine and the Rho kinase inhibitors Y-27632 and hydroxyfasudil induced a similar relaxation when mature pDA were stimulated with O2 or H2O2. Moreover, the sensitivity to these drugs increased with maturation. Our results indicate the presence of a common mechanism for O2 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 O2 sensitivity appearance during development. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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