High-Salt Diet Inhibits Expression of Angiotensin Type 2 Receptor in Resistance Arteries

Abstract

Abstract-Recent studies suggested that type 2 angiotensin receptor (AT2R) could contribute to regulation of blood pressure and/or vascular remodeling. A key question relates to the effects of potential modulators of vascular AT2R expression. In the present work, we evaluated if high salt intake (70 mmol/L NaCl in drinking water) could modulate rat mesenteric artery AT2R function and expression. Angiotensin II dose-response curves were studied in rat perfused pressurized small-diameter arteries in the presence of losartan (AT1R antagonist Key Words: mineralocorticoid Ⅲ sodium Ⅲ hypertension Ⅲ vascular remodeling Ⅲ apoptosis T he renin-angiotensin-aldosterone system (RAAS) regulates vascular tone, body fluid volume, electrolyte balance, hormonal secretion, and neuronal activity. The biological effects of angiotensin II (Ang II), the main effector peptide in the vasculature, are mediated by at least 2 receptor isofoms. 1,2 The type 1 receptor (AT1R) mediates vasoconstriction, sympathetic facilitation, and trophic effects. The type 2 receptor (AT2R) is widely expressed during fetal development, whereas in the adult its expression has been detected in many different vessel types, including mesenteric, coronary, and renal arteries. 3-6 AT2R has opposite effects to those of AT1R, ie, it promotes cell apoptosis and inhibits cell proliferation. 6,7 AT2R also attenuates the pressor action of Ang II 8 and mediates vasodilation. 9,10 Recently, it has been shown that Ang II relaxes small mesenteric arteries via AT2R when AT1R are blocked. [11][12][13] Interestingly, the expression of AT2R is increased in several pathologic conditions such as vascular injury, 14 cardiac remodeling, congestive heart failure, and myocardial infarction. 15,16 It has been suggested that in adults the presence of AT2R in vascular tissues may be playing a role in vascular tone and/or tissue remodeling. [17][18][19] Therefore, a key and complex question that arises is how AT1R and AT2R expression are modulated. Several studies indicate interaction between Ang II and aldosterone, affecting the expression of ATRs. The expression of AT1R appears to be induced by Ang II in vascular smooth muscle, 4 and mineralocorticoids potentiate the action of Ang II in cultured rat vascular smooth muscle cells (VSMCs) by increasing the number of AT1R. 20,21 However, there are few data concerning the physiological regulation of AT2R expression. Dietary sodium depletion, which increases RAAS activity, enhances renal AT2 receptor function 10,22 and expression in both young and mature adult rats, mainly in the glomeruli and interstitial cells. 23 Induction of AT2R-mediated modulation of blood pressure was described in rats fed with a synthetic diet, an effect attributed to the stimulation of the RAAS. 8 Bonnet et al 24 have shown that Ang II infusion in the rat induces the expression of AT2R in the mesenteric vasculature. Nevertheless, it is not clear whether Ang II directly mediates the increased AT2R expression or if it is secondary to direct aldosterone action on arte...

Endothelial Epithelial Sodium Channel Inhibition Activates Endothelial Nitric Oxide Synthase via Phosphoinositide 3-Kinase/Akt in Small-Diameter Mesenteric Arteries

“…13,14 External artery diameter was determined by videomicroscopy. Vasodilatory responses to shear stress were measured according to Matrougui et al 15 Isometric tension studies were performed according to Rahman et al.…”

“…Kidney and mesenteric arteries were processed for total RNA extraction, 14 and PCRs were carried out with specifics primers for rat ENaC subunits.…”

A Single Initiating Cause of Hypertension; Potential for Primary Prevention

“…High salt diet has been shown to inhibit the expression of AT2r [86] and it is proposed that EGF release from its precursor via mechanotransduction is less efficient in the presence of high salt intake. The inhibition of Pathway 1 leads to the dominance of Pathway 2 (AT1r).…”

Recombinant adeno-associated virus-mediated delivery of antisense angiotensin II receptor 1 gene attenuates hypertension development

“…It has been demonstrated that the renin-angiotensin (RAS) is important in the development and maintenance of hypertension in both essential hypertensive patients and animal models of hypertension [5,6] . Moreover, many studies have revealed that high salt could stimulate the RAS and induce angiotensin II receptor 1 (AT 1 R) overexpression, which may be responsible for the elevation of blood pressure [7,8] . The blockade or interruption of RAS by pharmacological agents, such as the angiotensin-converting enzyme inhibitor and AT 1 R antagonists, have been extremely successful in the treatment of hypertension and the prevention of it complications.…”