Vogt Liffert, Cunha Vitória, Dominiczak Anna F, Grassi Guido, Rajzer Marek, Virdis Agostino, Weber Thomas
Department of Internal Medicine, Section Nephrology, Amsterdam UMC, Location AMC, the Netherlands (L.V.).
Amsterdam Cardiovascular Sciences, University of Amsterdam, the Netherlands (L.V.).
Hypertension. 2025 Aug 5. doi: 10.1161/HYPERTENSIONAHA.125.24002.
Traditionally, the kidney has been thought to play a key role in the development of hypertension. Disturbed sodium regulatory pathways can lead to primary hypertension, with abnormalities in the pressure-natriuresis mechanism contributing to its onset. An adverse intrauterine environment and postnatal stressors can affect nephron number, further linking renal development to hypertension risk. The development of hypertension may, however, also be influenced by alternative factors beyond the kidney. Monogenic diseases and polygenic risk scores are associated with hypertension development. Epigenetic mechanisms can influence the phenotype of the vascular endothelium in response to environmental stimuli, potentially leading to changes in blood pressure. Regulation of vascular tone, microvascular rarefaction, and interactions with the immune system are other nonrenal factors contributing to hypertension. The exposome, including air pollution and noise, has its impact already before conception via maternal and paternal influences, as well as later in life. In addition, lifestyle factors such as sodium and alcohol intake and tobacco use have been linked to hypertension through mechanisms such as increased sympathetic activity and vasoconstriction, highlighting the importance of behavioral factors in hypertension development. Age-related stiffening becomes important in later life, influences blood pressure phenotype, and may even precede hypertension development. Considering these multiple contributors, relevant for pathophysiology, prevention, and management of hypertension, the question arises whether the kidney-centered view on hypertension is sufficient or whether a more integrative, multifactorial perspective is needed. Full understanding of renal and nonrenal factors and their interactions driving hypertension is crucial to curb the global burden of this disease.
传统上，人们认为肾脏在高血压的发生发展中起关键作用。钠调节途径紊乱可导致原发性高血压，压力-利钠机制异常促成其发病。不良的子宫内环境和产后应激源可影响肾单位数量，进一步将肾脏发育与高血压风险联系起来。然而，高血压的发生发展也可能受到肾脏以外的其他因素影响。单基因疾病和多基因风险评分与高血压的发生发展相关。表观遗传机制可影响血管内皮细胞对环境刺激的表型反应，可能导致血压变化。血管张力调节、微血管稀疏以及与免疫系统的相互作用是导致高血压的其他非肾脏因素。暴露组，包括空气污染和噪音，在受孕前就通过母体和父体影响产生作用，在生命后期也有影响。此外，钠和酒精摄入以及吸烟等生活方式因素通过交感神经活动增加和血管收缩等机制与高血压相关联，凸显了行为因素在高血压发生发展中的重要性。与年龄相关的血管硬化在生命后期变得重要，影响血压表型，甚至可能先于高血压的发生。考虑到这些与高血压的病理生理学、预防和管理相关的多种因素，就产生了一个问题，即以肾脏为中心的高血压观点是否足够，还是需要一个更综合、多因素的视角。全面了解驱动高血压的肾脏和非肾脏因素及其相互作用对于控制这种疾病的全球负担至关重要。
