Agren Pia, Cogolludo Angel L, Kessels Carolina G A, Pérez-Vizcaíno Francisco, De Mey Jo G R, Blanco Carlos E, Villamor Eduardo
Department of Pediatrics, Maastricht University Hospital, Research Institute Growth and Development (GROW), University of Maastricht, Maastricht, The Netherlands.
Am J Physiol Regul Integr Comp Physiol. 2007 Jan;292(1):R485-96. doi: 10.1152/ajpregu.00204.2006. Epub 2006 Aug 17.
The present study aimed to characterize the contractile reactivity of the chicken ductus arteriosus (DA) from the last stage of prenatal development and throughout the perinatal period. Isolated DA rings from 15-day, noninternally-pipped 19-day, and externally-pipped 21-day embryos were studied using myograph techniques. On embryonic day 15, the chicken DA did not respond to O(2) (0 to 21%), norepinephrine (NE), or phenylephrine (Phe) but contracted in response to high-K(+) solution, the inhibitor of voltage-gated channels 4-aminopyridine, U-46619, and endothelin (ET)-1. These responses increased with advancing incubation age. Contractile responses to O(2), NE, and Phe were present in the 19- and 21-day embryo. Oxygen-induced contraction was restricted to the pulmonary side of the DA and was augmented by the nitric oxide synthase inhibitor N(omega)-nitro-l-arginine methyl ester and the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and reduced by the peptidic ET(A) and ET(B)-receptor antagonist PD-142,893. Transmural electrical stimulation of nerves, the nonselective cyclooxygenase (COX) inhibitor indomethacin, the COX-1 inhibitor valeryl salicylate, the COX-2 inhibitor nimesulide, the inhibitor of ATP-sensitive K(+) channels glibenclamide, and the inhibitor of Ca(2+)-activated K(+) channels tetraethylammonium did not cause contraction of the DA rings at any age. We conclude that transition to ex ovo life is accompanied by dramatic changes in chicken DA reactivity. At 0.7 incubation, excitation-contraction and pharmacomechanical coupling for several contractile agonists are already present, whereas the constrictor effects of O(2) and cathecolamines appear later in development and are located in the pulmonary side of the DA.
本研究旨在描述产前发育最后阶段及整个围产期鸡动脉导管(DA)的收缩反应性。使用肌张力测定技术研究了来自15天、未破壳的19天和已破壳的21天胚胎的分离DA环。在胚胎第15天,鸡DA对O₂(0%至21%)、去甲肾上腺素(NE)或苯肾上腺素(Phe)无反应,但对高钾溶液、电压门控通道抑制剂4-氨基吡啶、U-46619和内皮素(ET)-1有收缩反应。这些反应随着孵化年龄的增加而增强。对O₂、NE和Phe的收缩反应在19天和21天胚胎中存在。氧气诱导的收缩局限于DA的肺侧,一氧化氮合酶抑制剂Nⁿ-硝基-L-精氨酸甲酯和可溶性鸟苷酸环化酶抑制剂1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮可增强该收缩反应,而肽类ET(A)和ET(B)受体拮抗剂PD-142,893可使其减弱。神经的跨壁电刺激、非选择性环氧化酶(COX)抑制剂吲哚美辛、COX-1抑制剂戊酰水杨酸、COX-2抑制剂尼美舒利、ATP敏感性钾通道抑制剂格列本脲以及钙激活钾通道抑制剂四乙铵在任何年龄均未引起DA环收缩。我们得出结论,向体外生活的转变伴随着鸡DA反应性的显著变化。在孵化0.7时,几种收缩激动剂的兴奋-收缩和药理机械偶联已经存在,而O₂和儿茶酚胺的收缩作用在发育后期出现,且位于DA的肺侧。