Endothelium-dependent responses in coronary arteries are changed with puberty in male pigs
Endothelium-dependent responses in coronary arteries are changed with puberty in male pigs
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DOI：
10.1152/ajpheart.00029.2003
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发表时间：
2003-09-01
影响因子：
4.8
通讯作者：
Miller, VM
中科院分区：
文献类型：
--
作者：
Chatrath, R;Ronningen, KL;Miller, VM
在人类中，心血管疾病始于成年早期，并且男性比女性更常见。然而，人们对男性向成年过渡期间的血管功能知之甚少。本研究的目的是确定青春期期间内皮源性一氧化氮 (NO) 产生的变化和冠状动脉反应。从幼年（2-3月龄）和成年（5-6月龄）雄性猪（n = 8/组）收集血浆用于测量NO，并收集主动脉内皮细胞用于测量内皮NO合酶（eNOS）的mRNA和蛋白质。虽然幼年公猪的血浆 NO (67.0 +/- 25.6 muM) 高于成年公猪 (15.0 +/- 7.1 muM)，但两组的 eNOS 蛋白相似。然而，幼猪主动脉内皮细胞中 eNOS mRNA 水平较低。在悬挂在器官室中用于测量等长力并用PGF（2α）收缩的冠状动脉环中，仅在幼年猪中吲哚美辛显着抑制对α（2）-肾上腺素能激动剂的松弛[EC50（-log M），吲哚美辛为6.7 +/- 0.3，对照条件下为7.7 +/- 0.3]。 N-G-单甲基-L-精氨酸（L-NMMA）抑制两组的松弛。相反，在存在吲哚美辛的情况下，缓激肽的松弛仅在成年猪的动脉中被L-NMMA抑制[EC50(-logM)，吲哚美辛为8.9+/-0.3，添加L-NMMA为8.6+/-0.3]。这些结果表明，与性成熟相关的激素变化可能会影响 eNOS 蛋白的转录后和/或翻译调节，并导致成年雄性猪血浆 NO 降低。此外，内皮衍生的抑制性环氧合酶产物似乎在青少年中占主导地位。
In humans, cardiovascular disease begins in young adulthood and is more prevalent in males than females. However, little is known about vascular function during transition to adulthood in males. The aim of this study was to define changes in production of endothelium-derived nitric oxide (NO) and coronary arterial responses during puberty. Plasma was collected from juvenile (2-3 mo of age) and adult (5-6 mo of age) male pigs (n = 8/group) for measurement of NO, and aortic endothelial cells were collected for measurement of mRNA and protein for endothelial NO synthase ( eNOS). Although plasma NO was higher in juvenile (67.0 +/- 25.6 muM) than in adult (15.0 +/- 7.1 muM) male pigs, eNOS protein was similar in both groups. However, levels of mRNA for eNOS were lower in aortic endothelial cells from juvenile pigs. In rings of coronary arteries suspended in organ chambers for measurement of isometric force and contracted with PGF(2alpha), relaxations to an alpha(2)-adrenergic agonist were significantly inhibited by indomethacin only in juvenile pigs [EC50 ( - log M), 6.7 +/- 0.3 with indomethacin and 7.7 +/- 0.3 under control conditions]. N-G-monomethyl-L- arginine (L-NMMA) inhibited relaxations in both groups. On the contrary, in the presence of indomethacin, relaxations to bradykinin were inhibited by L-NMMA only in arteries from adult pigs [EC50 (- log M), 8.9 +/- 0.3 with indomethacin and 8.6 +/- 0.3 with addition of L-NMMA]. These results suggest that hormonal changes associated with sexual maturity may affect posttranscriptional and/or translational regulation of eNOS protein and result in lower plasma NO in adult male pigs. In addition, endothelium-derived inhibitory cyclooxygenase products seem to predominate in juveniles.