Bomfim Guilherme Henrique Souza, Méndez-López Iago, Fernández-Morales José Carlos, Padín Juan Fernando, Jurkiewicz Aron, Jurkiewicz Neide Hyppolito, García Antonio García
Instituto Teófilo Hernando, Universidad Autónoma de Madrid, Madrid, Spain; Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Spain; Departamento de Farmacologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil.
Instituto Teófilo Hernando, Universidad Autónoma de Madrid, Madrid, Spain; Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
Eur J Pharmacol. 2017 May 15;803:65-77. doi: 10.1016/j.ejphar.2017.03.017. Epub 2017 Mar 16.
It is known that chronic ethanol (EtOH) consumption leads to hypertension development and has been associated with deleterious effects on the cardiovascular system. Whether this condition alters calcium (Ca) signaling and exocytosis in adrenal chromaffin cells (CCs) as the case is for genetic hypertension, is unknown. We explored this question in four randomized experimental groups, male Wistar Kyoto (WKY/EtOH) and Spontaneously Hypertensive (SHR/EtOH) rats were subjected to the intake of increasing EtOH concentrations (5-20%, for 30 days) and their respective controls (WKY/Control and SHR/Control) received water. WKY/EtOH developed hypertension and cardiac hypertrophy; blood aldehyde dehydrogenase (ALDH) and HO were also augmented. In comparison with WKY/Control, CCs from WKY/EtOH had the following features: (i) depolarization and higher frequency of spontaneous action potentials; (ii) decreased Ca currents with slower inactivation; (iii) decreased K currents; (iv) augmented K-elicited cytosolic Ca transients ([Ca]); (v) enhanced K-elicited catecholamine release. These cardiovascular, blood and CCs changes were qualitatively similar to those undergone by SHR/Control and SHR/EtOH. The results suggest that the hypertension elicited by chronic EtOH has pathogenic features common to genetic hypertension namely, augmented [Ca] transients and catecholamine release from their CCs.
已知长期摄入乙醇（EtOH）会导致高血压，并与心血管系统的有害影响有关。这种情况是否像遗传性高血压那样改变肾上腺嗜铬细胞（CCs）中的钙（Ca）信号传导和胞吐作用尚不清楚。我们在四个随机实验组中探讨了这个问题，雄性Wistar Kyoto（WKY/EtOH）和自发性高血压（SHR/EtOH）大鼠摄入浓度逐渐增加的EtOH（5%-20%，持续30天），它们各自的对照组（WKY/对照和SHR/对照）则饮水。WKY/EtOH组出现了高血压和心脏肥大；血液中的醛脱氢酶（ALDH）和HO也增加了。与WKY/对照相比，WKY/EtOH组的CCs具有以下特征：（i）去极化和更高频率的自发动作电位；（ii）Ca电流降低且失活较慢；（iii）K电流降低；（iv）K引发的胞质Ca瞬变（[Ca]）增加；（v）K引发儿茶酚胺释放增强。这些心血管、血液和CCs的变化在性质上与SHR/对照和SHR/EtOH组所经历的变化相似。结果表明，慢性EtOH引起的高血压具有与遗传性高血压相同的致病特征，即[Ca]瞬变增加以及CCs释放儿茶酚胺增加。
