Recent Advances in Understanding the Molecular Pathophysiology of Angiotensin II Receptors: Lessons From Cell-Selective Receptor Deletion in Mice

Milestone Papers on Signal Transduction Mechanisms of Hypertension and Its Complications

“…These findings indicate that the molecular mechanism leading to Ang II-induced vascular remodeling involving inflammatory perivascular fibrosis does not require vascular hemodynamic stress during the early stages of hypertension. 18 These findings, thus, advance our knowledge of the Ang II-infused mouse model of hypertension in which vascular remodeling and hypertension were mechanistically separated enabling a new interpretation for given phenotypes on specific manipulation (Figure 2). Drug screening is also possible to look for compounds to mitigate vascular remodeling with no alteration in blood pressure phenotype.…”

“…Detailed discussions were provided in the Supplemental Material 2,15,[17][18][19][20][21][22][23][24][25][26][27][28][29] and Figure S1 with supporting versus opposing findings about this point and cell type-specific roles of AT 1 R in hypertension, vascular remodeling, and AAA. 18 In addition, some of the most exciting recent publications on the noncanonical RAS components, extra-renal actions of mineralocorticoid receptors, and the singlecell transcriptomics report with Ang II infusion are discussed in the Supplemental Material. [30][31][32][33] Overall, these findings significantly advance our understanding of RAS-mediated hypertension and associated cardiovascular remodeling.…”

“…In addition, proximal tubule AT 1 R (PT-AT 1 R) is essential for Ang II-induced hypertension by mediating the enhancement of salt and water reabsorption. 18 both primary and secondary forms of hypertension are known to be associated with elevated vascular resistance though its causal role remains poorly defined, as the triggering factor(s) and the ensuing mechanisms that lead to increased vascular resistance before blood pressure rise are not well established. Until recently, only arterioles and small arteries with lumen diameter <150 µm were generally considered resistance arteries capable of generating a myogenic, contractile response to wall stretch from changes in intraluminal pressure.…”

The role of hormones in ILC2‐driven allergic airway inflammation

“…Angiotensin II (Ang II) is a peptide hormone with potent vasoconstrictor activity upon binding to angiotensin type 1 receptor (AT1) and angiotensin type 2 receptor (AT2). 86,87 Ang II is converted from angiotensinogen under the sequential regulation of renin and angiotensin-converting enzyme (ACE) in the renin-angiotensin system (RAS). 87 Interestingly, the mRNA levels of a variety of RAS components, such as renin, angiotensinogen and ACE, are significantly elevated in lung epithelial cells following papain challenge.…”

Phenotypic switching of vascular smooth muscle cells in atherosclerosis, hypertension, and aortic dissection

“…Ang II is well-known to contribute to physiological and pathological aspects of VSMC behavior. These cells express two receptors, type 1 (AT1) and 2 (AT2), which are the primary targets of Ang II on the cell surface of VSMCs (Ardaillou, 1999;Eguchi et al, 2023). While AT1 is primarily implicated in VSMC contraction (Hughes, 1998;Yu et al, 2012), a characteristic of differentiated phenotype, AT2 is known to promote proliferation or hypertrophy of these cells (Chow & Allen, 2016;Lemarié & Schiffrin, 2010;Nguyen Dinh Cat & Touyz, 2011;Ruiz-Ortega et al, 2003).…”