Integration of purinergic and angiotensin II receptor function in renal vascular responses and renal injury in angiotensin II-dependent hypertension

Purinergic signalling

article

Martha Franco¹  Oscar Pérez-Méndez²  Supaporn Kulthinee³  L. Gabriel Navar³ 

[1] Department of Nephrology, Renal Pathophysiology Laboratory, Instituto Nacional de Cardiología “Ignacio Chávez”;Department Molecular Biology, Instituto Nacional de Cardiología “Ignacio Chávez”;Department of Physiology and Hypertension and Renal Center, Tulane University School of Medicine;Department of Cardiovascular and Thoracic Technology, Chulabhorn International College of Medicine, Thammasat University

关键词: Hypertension;    ATP;    P2X antagonists;    Purinergic P2X receptors;    Angiotensin II;    Renal hemodynamics;    AT1 receptor antagonists;   

DOI  :  10.1007/s11302-019-09662-5

学科分类：分子生物学，细胞生物学和基因

来源: Springer

【 摘 要 】

Glomerular arteriolar vasoconstriction and tubulointerstitial injury are observed before glomerular damage occurs in models of hypertension. High interstitial ATP concentrations, caused by the increase in arterial pressure, alter renal mechanisms involved in the long-term control of blood pressure, autoregulation of glomerular filtration rate and blood flow, tubuloglomerular feedback (TGF) responses, and sodium excretion. Elevated ATP concentrations and augmented expression of P2X receptors have been demonstrated under a genetic background or induction of hypertension with vasoconstrictor peptides. In addition to the alterations of the microcirculation in the hypertensive kidney, the vascular actions of elevated intrarenal angiotensin II levels may be mitigated by the administration of broad purinergic P2 antagonists or specific P2Y12, P2X1, and P2X7 receptor antagonists. Furthermore, the prevention of tubulointerstitial infiltration with immunosuppressor compounds reduces the development of salt-sensitive hypertension, indicating that tubulointerstitial inflammation is essential for the development and maintenance of hypertension. Inflammatory cells also express abundant purinergic receptors, and their activation by ATP induces cytokine and growth factor release that in turn contributes to augment tubulointerstitial inflammation. Collectively, the evidence suggests a pathophysiological activation of purinergic P2 receptors in angiotensin-dependent hypertension. Coexistent increases in intrarenal angiotensin II and activates Ang II AT1 receptors, which interacts with over-activated purinergic receptors in a complex manner, suggesting convergence of their post-receptor signaling processes.

【 授权许可】

CC BY