Moreau J M, Messenger S A, Ciriello J
Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London N6A 5C1, Canada.
Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London N6A 5C1, Canada.
Neuroscience. 2015 Dec 3;310:430-41. doi: 10.1016/j.neuroscience.2015.09.066. Epub 2015 Oct 9.
Angiotensin II (ANG II) is known to promote leptin production and secretion. Although ANG II type 1 receptors (AT1Rs) and leptin are expressed within the carotid body, it is not known whether AT1R and leptin are co-expressed in the same glomus cells nor if these peptides are affected within the carotid body by intermittent hypoxia (IH). This study was done to investigate whether ANG II modulated leptin signaling in the carotid body during IH. Rats were treated with captopril (Capt) or the AT1R blocker losartan (Los) in the drinking water for 3days prior to being exposed to IH (8h) or normoxia (8h). IH induced increases in plasma ANG II and leptin compared to normoxic controls. Capt treatment abolished the plasma leptin changes to IH, whereas Los treatment had no effect on the IH induced increase in plasma leptin. Additionally, carotid body glomus cells containing both leptin and the long form of the leptin receptor (OB-Rb) were found to co-express AT1R protein, and IH increased the expression of only AT1R protein within the carotid body in both Capt- and non-Capt-treated animals. On the other hand, Los treatment did not modify AT1R protein expression to IH. Additionally, Capt and Los treatment eliminated the elevated carotid body leptin protein expression, and the changes in phosphorylated signal transducer and activator of transcription three protein, the short form of the leptin receptor (OB-R100), suppressor of cytokine signaling 3, and phosphorylated extracellular-signal-regulated kinase 1/2 protein expression induced by IH. However, Capt elevated the expression of OB-Rb protein, whereas Los abolished the changes in OB-Rb protein to IH. These findings, taken together with the previous observation that ANG II modifies carotid body chemosensitivity, suggest that the increased circulating levels of ANG II and leptin induced by IH act at the carotid body to alter leptin signaling within the carotid body which in turn may influence chemoreceptor function.
已知血管紧张素II（ANG II）可促进瘦素的产生和分泌。尽管1型血管紧张素II受体（AT1Rs）和瘦素在颈动脉体中均有表达，但尚不清楚AT1R和瘦素是否在同一球细胞中共表达，也不清楚这些肽在颈动脉体内是否会受到间歇性缺氧（IH）的影响。本研究旨在探讨在间歇性缺氧期间ANG II是否调节颈动脉体中的瘦素信号传导。在暴露于间歇性缺氧（8小时）或常氧（8小时）之前，大鼠在饮用水中接受卡托普利（Capt）或AT1R阻滞剂氯沙坦（Los）治疗3天。与常氧对照组相比，间歇性缺氧诱导血浆ANG II和瘦素增加。Capt治疗消除了血浆瘦素对间歇性缺氧的变化，而Los治疗对间歇性缺氧诱导的血浆瘦素增加没有影响。此外，发现同时含有瘦素和瘦素受体长型（OB-Rb）的颈动脉体球细胞共表达AT1R蛋白，并且在接受Capt治疗和未接受Capt治疗的动物中，间歇性缺氧均增加了颈动脉体内仅AT1R蛋白的表达。另一方面，Los治疗并未改变间歇性缺氧时AT1R蛋白的表达。此外，Capt和Los治疗消除了颈动脉体瘦素蛋白表达的升高，以及间歇性缺氧诱导的磷酸化信号转导和转录激活因子3蛋白、瘦素受体短型（OB-R100）、细胞因子信号传导抑制因子3和磷酸化细胞外信号调节激酶1/2蛋白表达的变化。然而，Capt提高了OB-Rb蛋白的表达，而Los消除了间歇性缺氧时OB-Rb蛋白的变化。这些发现与之前观察到的ANG II改变颈动脉体化学敏感性的结果相结合，表明间歇性缺氧诱导的循环ANG II和瘦素水平升高作用于颈动脉体，改变颈动脉体内的瘦素信号传导，进而可能影响化学感受器功能。
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