Cerrudo Carolina S, Cavallero Susana, Rodríguez Fermepín Martín, González Germán E, Donato Martín, Kouyoumdzian Nicolás M, Gelpi Ricardo J, Hertig Cecilia M, Choi Marcelo R, Fernández Belisario E
Facultad de Farmacia y Bioquímica, Cátedras de Fisiopatología y Anatomía e Histología, Universidad de Buenos Aires, Buenos Aires, Argentina.
Facultad de Medicina, CONICET, Instituto de Fisiopatología Cardiovascular, Universidad de Buenos Aires, Buenos Aires, Argentina.
Front Physiol. 2021 May 25;12:651246. doi: 10.3389/fphys.2021.651246. eCollection 2021.
The involvement of natriuretic peptides was studied during the hypertrophic remodeling transition mediated by sequential exposure to chronic hemodynamic overload. We induced hypertension in rats by pressure (renovascular) or volume overload (DOCA-salt) during 6 and 12 weeks of treatment. We also studied the consecutive combination of both models in inverse sequences: RV 6 weeks/DS 6 weeks and DS 6 weeks/RV 6 weeks. All treated groups developed hypertension. Cardiac hypertrophy and left ventricular ANP gene expression were more pronounced in single DS than in single RV groups. BNP gene expression was positively correlated with left ventricular hypertrophy only in RV groups, while ANP gene expression was positively correlated with left ventricular hypertrophy only in DS groups. Combined models exhibited intermediate values between those of single groups at 6 and 12 weeks. The latter stimulus associated to the second applied overload is less effective than the former to trigger cardiac hypertrophy and to increase ANP and BNP gene expression. In addition, we suggest a correlation of ANP synthesis with volume overload and of BNP synthesis with pressure overload-induced hypertrophy after a prolonged treatment. Volume and pressure overload may be two mechanisms, among others, involved in the differential regulation of ANP and BNP gene expression in hypertrophied left ventricles. Plasma ANP levels reflect a response to plasma volume increase and volume overload, while circulating BNP levels seem to be regulated by cardiac BNP synthesis and ventricular hypertrophy.
在由连续暴露于慢性血流动力学过载介导的肥厚性重塑转变过程中，对利钠肽的参与情况进行了研究。在6周和12周的治疗期间，我们通过压力（肾血管性）或容量过载（去氧皮质酮-盐）诱导大鼠高血压。我们还以相反顺序研究了两种模型的连续组合：肾血管性高血压6周/去氧皮质酮-盐6周和去氧皮质酮-盐6周/肾血管性高血压6周。所有治疗组均出现高血压。与单纯肾血管性高血压组相比，单纯去氧皮质酮-盐组的心脏肥大和左心室心钠素（ANP）基因表达更为明显。仅在肾血管性高血压组中，脑钠肽（BNP）基因表达与左心室肥大呈正相关，而仅在去氧皮质酮-盐组中，心钠素基因表达与左心室肥大呈正相关。在6周和12周时，联合模型表现出介于单一组之间的中间值。与第二次施加的过载相关的后一种刺激在触发心脏肥大以及增加心钠素和脑钠肽基因表达方面比前一种刺激效果更差。此外，我们认为在长期治疗后，心钠素的合成与容量过载相关，而脑钠肽的合成与压力过载诱导的肥大相关。容量和压力过载可能是参与肥厚左心室中心钠素和脑钠肽基因表达差异调节的两种机制，其他机制还有很多。血浆心钠素水平反映了对血浆容量增加和容量过载的反应，而循环脑钠肽水平似乎受心脏脑钠肽合成和心室肥大的调节。
