Supplemental Digital Content is available in the text. Cardiac hypertrophy and renal damage associated with hypertension are independent predictors of morbidity and mortality. In a model of hypertensive heart disease and renal damage, we tested the actions of continuous administration of Vastiras, a novel compound derived from the linear fragment of ANP (atrial natriuretic peptide), namely pro-ANP31–67, on blood pressure and associated renal and cardiac function and remodeling. Of note, this peptide, unlike the ring structured forms, does not bind to the classic natriuretic peptide receptors. Dahl/Salt–Sensitive rats fed a 4% NaCl diet for 6 weeks developed hypertension, cardiac hypertrophy, and renal damage. Four weeks of treatment with 50 to 100 ng/kg per day of Vastiras exhibited positive effects on renal function, independent of blood pressure regulation. Treated rats had increased urine excretion, natriuresis, and enhanced glomerular filtration rate. Importantly, these favorable renal effects were accompanied by improved cardiac structure and function, including attenuated cardiac hypertrophy, as indicated by decreased heart weight to body weight ratio, relative wall thickness, and left atrial diameter, as well as reduced fibrosis and normalized ratio of the diastolic mitral inflow E wave to A wave. A renal subtherapeutic dose of Vastiras (25 ng/kg per day) induced similar protective effects on the heart. At the cellular level, cardiomyocyte size and t-tubule density were preserved in Vastiras-treated compared with untreated animals. In conclusion, these data demonstrate the cardiorenal protective actions of chronic supplementation of a first-in-class compound, Vastiras, in a preclinical model of maladaptive cardiac hypertrophy and renal damage induced by hypertension.

中文翻译：

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新型复合 Vastiras 在终末器官损伤的临床前模型中的心脏保护作用

补充数字内容在文本中可用。与高血压相关的心脏肥大和肾损害是发病率和死亡率的独立预测因子。在高血压心脏病和肾损伤模型中，我们测试了连续给药 Vastiras 的作用，Vastiras 是一种衍生自 ANP（心房利钠肽）线性片段的新型化合物，即 pro-ANP31-67，对血压和相关肾病的影响。和心脏功能和重塑。值得注意的是，这种肽与环状结构形式不同，不与经典的利钠肽受体结合。Dahl/盐敏感性大鼠喂食 4% NaCl 饮食 6 周后会出现高血压、心脏肥大和肾损伤。每天以 50 至 100 ng/kg 的 Vastiras 治疗 4 周对肾功能表现出积极作用，独立于血压调节。接受治疗的大鼠尿液排泄增加，尿钠排泄增加，肾小球滤过率增加。重要的是，这些有利的肾脏效应伴随着心脏结构和功能的改善，包括减弱的心脏肥大，如心脏重量与体重之比、相对壁厚和左心房直径降低以及纤维化减少和正常化比率所表明的舒张期二尖瓣流入 E 波到 A 波。肾脏亚治疗剂量的 Vastiras（每天 25 ng/kg）对心脏产生类似的保护作用。在细胞水平上，与未处理的动物相比，Vastiras 处理的心肌细胞大小和 t 小管密度保持不变。综上所述，