Ferreira Anna Rebeka Oliveira, Ribeiro Maiara Vanusa Guedes, Peres Maria Natalia Chimirri, Piovan Silvano, Gonçalves Géssica Dutra, Saavedra Lucas Paulo Jacinto, Martins Juliana Nunes de Lima, Junior Marcos Divino Ferreira, Cavalcante Keilah Valeria Naves, Lopes Gabriel Kian Guimarães, Carneiro Mariane, Almeida Douglas Lopes, Gomes Rodrigo Mello, Comar Jurandir Fernando, Armitage James Andrew, Mathias Paulo Cezar de Freitas, Palma-Rigo Kesia
Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringa, Maringa, Brazil.
Laboratory of Liver Metabolism and Radioisotopes, Department of Biochemistry, State University of Maringa, Maringa, Brazil.
Front Physiol. 2022 Apr 28;13:840179. doi: 10.3389/fphys.2022.840179. eCollection 2022.
Perturbations to nutrition during critical periods are associated with changes in embryonic, fetal or postnatal developmental patterns that may render the offspring more likely to develop cardiovascular disease in later life. The aim of this study was to evaluate whether autonomic nervous system imbalance underpins in the long-term hypertension induced by dietary protein restriction during peri-pubertal period. Male Wistar rats were assigned to groups fed with a low protein (4% protein, LP) or control diet (20.5% protein; NP) during peri-puberty, from post-natal day (PN) 30 until PN60, and then all were returned to a normal protein diet until evaluation of cardiovascular and autonomic function at PN120. LP rats showed long-term increased mean arterial pressure ( = 0.002) and sympathetic arousal; increased power of the low frequency (LF) band of the arterial pressure spectral ( = 0.080) compared with NP animals. The depressor response to the ganglion blocker hexamethonium was increased in LP compared with control animals ( = 0.006). Pulse interval variability showed an increase in the LF band and LF/HF ratio ( = 0.062 and = 0.048) in LP animals. The cardiac response to atenolol and/or methylatropine and the baroreflex sensitivity were similar between groups. LP animals showed ventricular hypertrophy ( = 0.044) and increased interstitial fibrosis ( = 0.028) compared with controls. Reduced protein carbonyls (PC) ( = 0.030) and catalase activity ( = 0.001) were observed in hearts from LP animals compared with control. In the brainstem, the levels of PC ( = 0.002) and the activity of superoxide dismutase and catalase ( = 0.044 and = 0.012) were reduced in LP animals, while the levels of GSH and total glutathione were higher ( = 0.039 and = 0.038) compared with NP animals. Protein restriction during peri-pubertal period leads to hypertension later in life accompanied by sustained sympathetic arousal, which may be associated with a disorganization of brain and cardiac redox state and structural cardiac alteration.
关键时期的营养紊乱与胚胎、胎儿或产后发育模式的变化有关，这些变化可能使后代在以后的生活中更容易患心血管疾病。本研究的目的是评估自主神经系统失衡是否是青春期前后饮食蛋白质限制所致长期高血压的基础。将雄性Wistar大鼠分为两组，在青春期前后（从出生后第30天到第60天）分别给予低蛋白饮食（4%蛋白质，LP）或对照饮食（20.5%蛋白质；NP），然后所有大鼠恢复正常蛋白质饮食，直到在出生后第120天评估心血管和自主神经功能。与NP组动物相比，LP组大鼠表现出长期平均动脉压升高（P = 0.002）和交感神经兴奋；动脉压频谱低频（LF）带功率增加（P = 0.080）。与对照动物相比，LP组对神经节阻滞剂六甲铵的降压反应增强（P = 0.006）。LP组动物的脉搏间期变异性显示LF带和LF/HF比值增加（P = 0.062和P = 0.048）。两组之间对阿替洛尔和/或甲基阿托品的心脏反应以及压力反射敏感性相似。与对照组相比，LP组动物表现出心室肥厚（P = 0.044）和间质纤维化增加（P = 0.028）。与对照组相比，LP组动物心脏中的蛋白质羰基（PC）含量降低（P = 0.030），过氧化氢酶活性降低（P = 0.001）。在脑干中，LP组动物的PC水平（P = 0.002）以及超氧化物歧化酶和过氧化氢酶活性降低（P = 0.044和P = 0.012），而与NP组动物相比，谷胱甘肽（GSH）和总谷胱甘肽水平更高（P = 0.039和P = 0.038）。青春期前后的蛋白质限制会导致后期高血压，并伴有持续的交感神经兴奋，这可能与脑和心脏氧化还原状态的紊乱以及心脏结构改变有关。
