AT(1) receptor-mediated augmentation of angiotensinogen, oxidative stress, and inflammation in ANG II-salt hypertension

作者：Lara Lucienne S; McCormack Michael; Semprum Prieto Laura C; Shenouda Sylvia; Majid Dewan S A; Kobori Hiroyuki; Navar L Gabriel; Prieto Minolfa C^*

来源：American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 2012, 302(1): F85-F94.

DOI：10.1152/ajprenal.00351.2011

• renin-angiotensin system
• reactive oxygen species
• kidney injury
• macrophage infiltration
• dihydroethidium staining

Lara LS, McCormack M, Semprum-Prieto LC, Shenouda S, Majid DS, Kobori H, Navar LG, Prieto MC. AT(1) receptor-mediated augmentation of angiotensinogen, oxidative stress, and inflammation in ANG II-salt hypertension. Am J Physiol Renal Physiol 302: F85-F94, 2012. First published September 7, 2011; doi:10.1152/ajprenal.00351.2011.-Augmentation of intrarenal angiotensinogen (AGT) synthesis, secretion, and excretion is associated with the development of hypertension, renal oxidative stress, and tissue injury during ANG II-dependent hypertension. High salt (HS) exacerbates hypertension and kidney injury, but the mechanisms remain unclear. In this study, we determined the consequences of HS intake alone compared with chronic ANG II infusion and combined HS plus ANG II on the stimulation of urinary AGT (uAGT), renal oxidative stress, and renal injury markers. Sprague-Dawley rats were subjected to 1) a normal-salt diet [NS, n = 5]; 2) HS diet [8% NaCl, n = 5]; 3) ANG II infusion in NS rats [ANG II 80 ng/min, n = 5]; 4) ANG II infusion in HS rats [ANG II+HS, n = 5]; and 5) ANG II infusion in HS rats treated with ANG II type 1 receptor blocker (ARB) [ANG II+HS+ARB, n = 5] for 14 days. Rats fed a HS diet alone did not show changes in systolic blood pressure (SBP), proteinuria, cell proliferation, or uAGT excretion although they did exhibit mesangial expansion, collagen deposition, and had increased NADPH oxidase activity accompanied by increased peroxynitrite formation in the kidneys. Compared with ANG II rats, the combination of ANG II infusion and a HS diet led to exacerbation in SBP (175 +/- 10 vs. 221 +/- 8 mmHg; P %26lt; 0.05), proteinuria (46 +/- 7 vs. 127 +/- 7 mg/day; P %26lt; 0.05), and uAGT (1,109 +/- 70 vs.. 7,200 +/- 614 ng/day; P %26lt; 0.05) associated with greater collagen deposition, mesangial expansion, interstitial cell proliferation, and macrophage infiltration. In both ANG II groups, the O-2(-) levels were increased due to increased NADPH oxidase activity without concomitant increases in peroxynitrite formation. The responses in ANG II rats were prevented or ameliorated by ARB treatment. The results indicate that HS independently stimulates ROS formation, which may synergize with the effect of ANG II to limit peroxynitrite formation, leading to exacerbation of uAGT and greater injury during ANG II salt hypertension.

• 出版日期2012-1