Classical Renin‐Angiotensin System in Kidney Physiology

Abstract

The renin-angiotensin system has powerful effects in control of the blood pressure and sodium homeostasis. These actions are coordinated through integrated actions in the kidney, cardio-vascular system and the central nervous system. Along with its impact on blood pressure, the renin-angiotensin system also influences a range of processes from inflammation and immune responses to longevity. Here, we review the actions of the “classical” renin-angiotensin system, whereby the substrate protein angiotensinogen is processed in a two-step reaction by renin and angiotensin converting enzyme, resulting in the sequential generation of angiotensin I and angiotensin II, the major biologically active renin-angiotensin system peptide, which exerts its actions via type 1 and type 2 angiotensin receptors. In recent years, several new enzymes, peptides, and receptors related to the renin-angiotensin system have been identified, manifesting a complexity that was previously unappreciated. While the functions of these alternative pathways will be reviewed elsewhere in this journal, our focus here is on the physiological role of components of the “classical” renin-angiotensin system, with an emphasis on new developments and modern concepts.

20-Hydroxyeicosatetraenoic Acid (HETE)-dependent Hypertension in Human Cytochrome P450 (CYP) 4A11 Transgenic Mice

“…Statistically significant changes are depicted by the p values. system in the kidney has the potential to increase sodium uptake (49). Consistent with this possibility, increased AGT mRNA expression was evident in kidneys of B-129/Sv-4A11 ϩ/ϩ mice compared with wild-type mice.…”

Vascular Type 1A Angiotensin II Receptors Control BP by Regulating Renal Blood Flow and Urinary Sodium Excretion

“…Activation of AT 1 receptors can trigger a cascade of physiologic responses, including vasoconstriction, activation of the sympathetic nervous system, and stimulation of sodium reabsorption by the kidney, which can conspire to promote hypertension and end-organ damage. 3 However, until recently, it has been difficult to unravel the relative contributions of these distinct AT 1 receptor responses to the pathogenesis of hypertension.…”

A Multicellular Vascular Model of the Renal Myogenic Response

“…Indeed, multiscale modeling that spans processes ranging from the subcellular up to the organ level is required to elucidate clinical and experimental findings such as the effects of integrins [31,32], epithelial sodium channels (ENaCs) [33,34], angiotensin II (AngII) [35][36][37][38], nitric oxide (NO) [39,40], and an array of other vasomodulators [41][42][43][44], or the pathophysiology associated with certain chronic conditions such as hypertension [45,46], diabetes mellitus [47,48], or chronic kidney disease [49,50]. Most of these previous studies have used simple compartmental models (Windkessels), ordinary or partial differential equations, and more recently, probabilistic methods for reproducing renal vascular networks [28].…”