Effects of sex and estrogen on chicken ductus arteriosus reactivity.

Sex hormones have an important influence on cardiovascular physiology and pathophysiology and sex differences in vascular reactivity have been widely demonstrated. In the present study we hypothesized 1) the presence of sexual dimorphism in chicken ductus arteriosus (DA) responsiveness to contractile and relaxant stimuli and 2) that estrogens are vasoactive in the chicken DA. In vitro contractions (assessed with a wire myograph) induced by normoxia, KCl, 4-aminopyridine, norepinephrine, phenylephrine, U46619, or endothelin-1, as well as relaxations induced by ACh, sodium nitroprusside, BAY 41-2272, PGE(2), isoproterenol, forskolin,Y-27632, and hydroxyfasudil were not significantly different between males and females. The estrogen 17beta-estradiol elicited concentration-dependent relaxation of KCl-, phenylephrine-, and oxygen-induced active tone in male and female chicken DA. The stereoisomer 17alpha-estradiol showed lesser relaxant effects, and the selective estrogen receptor (ER) agonists 4,4',4''-(4-propyl-[(1)H]pyrazole-1,3,5-triyl)tris-phenol (ERalpha) and 2,3-bis(4-hydroxyphenyl)-propionitrile (ERbeta) did not show any effect. There were no sex differences in the responses to estrogen. Endothelium removal or the presence of the soluble guanylate cyclase inhibitor ODQ, the K(+) channel blockers tetraethylammonium, glibenclamide, and charybdotoxin, or the ER antagonist fulvestrant did not modify 17beta-estradiol-induced relaxation. CaCl(2) (30 muM-10 mM) induced concentration-dependent contraction in DA rings depolarized by 62.5 mM KCl or stimulated with 21% O(2) in Ca(2+)-free medium. Preincubation with 17beta-estradiol or the L-type Ca(2+) channel blocker nifedipine produced an inhibition of CaCl(2)-induced contractions. In conclusion, there are no sex-related differences in chicken DA reactivity. The estrogen 17beta-estradiol induces an endothelium-independent relaxation of chicken DA that is not mediated by ER activation. This relaxant effect is, at least partially, due to inhibition of Ca(2+) entry from extracellular space.

Maturation of O2 sensing and signaling in the chicken ductus arteriosus.

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.

Third-degree atrioventricular block in an adolescent following acute alcohol intoxication.

Alcohol abuse is a major problem among adolescents, and has both acute, potentially lethal, and long-term harmful effects. The authors describe an adolescent who was in a subcomatose condition after binge drinking. His serum alcohol concentration was 3.7 g/l. The next morning, before transfer to the paediatric ward, he developed a third-degree atrioventricular (AV) block without cardiac output while his infusion needle was removed. This recovered spontaneously after a precordial thump. Retrospectively, electrocardiography showed an increasing PR prolongation (200-300 ms) before the removal of the infusion needle. ECG recordings several hours later showed a first-degree AV block, which was no longer seen during follow-up, 1 month later. The authors conclude that acute alcohol poisoning has the potential to prolong the PR interval in young, healthy adolescents without pre-existing first-degree AV block and provoke a third-degree AV block after vagal stimulation. It is yet another potential danger of acute alcohol intoxication in this age group.