Renal Generation of Angiotensin II and the Pathogenesis of Hypertension

Abstract

The existence of a complete and functional renin-angiotensin system along the nephron is widely recognized. However, its precise role in blood pressure control and, by extension, hypertension is still uncertain. While most investigators agree that overexpressing RAS components along the nephron results in hypertension, two important issues remain: whether the local RAS works as a separate entity or represents an extension of the systemic RAS and whether locally generated angiotensin II has specific renal effects on blood pressure that are distinct from systemic angiotensin II. This review addresses these issues while emphasizing the unique role of local angiotensin II in the response of the kidney to hypertensive stimuli and the induction of hypertension.

Maintaining Balance Under Pressure

“…33 With Gonzalez-Villalobos and colleagues, we examined the transporter profile in kidneys from mice with L-NAME hypertension. 16 In addition to low NO, this model exhibits low circulating AngII, elevated intrarenal AngII production and vasoconstriction. Thus, one might expect renal transporters stimulation in the absence of the NO, however, no distal transporter activation was evident.…”

Renin, Genes, MicroRNAs, and Renal Mechanisms Involved in Hypertension

“…27 Angiotensinogen in segments 1 and 2 of the proximal tubule seems to be of systemic origin, whereas angiotensinogen in segment 3 is produced locally. 12 Overexpression of tubular angiotensinogen raises BP. 28 …”

“…8,9 Recent reviews have highlighted the large body of experimental findings in support of abnormalities in renal processes being responsible for hypertension. [10][11][12][13] The involvement of an intrarenal renin-angiotensin system now seems to be an important component of the pathophysiological mechanisms involved in essential hypertension. [12][13][14][15][16][17][18][19] In the present review, I will first provide a brief summary of my earlier contributions to the hypertension field, these having been addressed in more detail in a review arising from my Lewis K. Dahl Memorial Lecture in 2010.…”

“…[10][11][12][13] The involvement of an intrarenal renin-angiotensin system now seems to be an important component of the pathophysiological mechanisms involved in essential hypertension. [12][13][14][15][16][17][18][19] In the present review, I will first provide a brief summary of my earlier contributions to the hypertension field, these having been addressed in more detail in a review arising from my Lewis K. Dahl Memorial Lecture in 2010. 20 I will then review my more recent research, which has involved the determination of alterations in gene expression at the transcriptome-wide level in hypertension and the pivotal mechanistic insights this work has provided, especially an intriguing mechanism controlling intrarenal renin.…”

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].…”