Effects of Resveratrol on the Renin-Angiotensin System in the Aging Kidney

Abstract

The renin-angiotensin system (RAS), especially the angiotensin II (Ang II)/angiotensin II type 1 receptor (AT1R) axis, plays an important role in the aging process of the kidney, through increased tissue reactive oxygen species production and progressively increased oxidative stress. In contrast, the angiotensin 1-7 (Ang 1-7)/Mas receptor (MasR) axis, which counteracts the effects of Ang II, is protective for end-organ damage. To evaluate the ability of resveratrol (RSV) to modulate the RAS in aging kidneys, eighteen-month-old male C57BL/6 mice were divided into two groups that received either normal mouse chow or chow containing resveratrol, for six months. Renal expressions of RAS components, as well as pro- and antioxidant enzymes, were measured and mouse kidneys were isolated for histopathology. Resveratrol-treated mice demonstrated better renal function and reduced albuminuria, with improved renal histologic findings. Resveratrol suppressed the Ang II/AT1R axis and enhanced the AT2R/Ang 1-7/MasR axis. Additionally, the expression of nicotinamide adenine dinucleotide phosphate oxidase 4, 8-hydroxy-2′-deoxyguanosine, 3-nitrotyrosine, collagen IV, and fibronectin was decreased, while the expression of endothelial nitric oxide synthase and superoxide dismutase 2 was increased by resveratrol treatment. These findings demonstrate that resveratrol exerts protective effects on aging kidneys by reducing oxidative stress, inflammation, and fibrosis, through Ang II suppression and MasR activation.

Redox signaling in aging kidney and opportunity for therapeutic intervention through natural products

“…Notably, a careful understanding of the underlying mechanisms about oxidative stress modulation is prerequisite before reaching clinical application as oxidant species are dynamically altered. Moreover, RAS, especially for angiotensin II/angiotensin II type 1 receptor axis, accelerated renal damage with aging via ROS generation [66], providing new insight into disease prevention.…”

“…Resveratrol [131,132], kaempferitrin [133] and chrysin [134] could reduce renal damage through AGE/RAGE or Nrf2-Keap1 in animal models of diabetic nephropathy. Additionally, resveratrol also played paramount roles in protecting against diabetic renal fibrosis [135], aging kidney [66] and kidney damage [136,137] in animal models. Nevertheless, the clinical application of resveratrol remains a tremendous challenge due to the unfavorable pharmacokinetic and biochemical properties, while resveratrol conjugates may portend a novel paradigm in the development of pharmaceutical exploitation, which has been proved to be more efficacious than resveratrol in human neuroblastoma SH-SY5Y cells [138].…”

The Regulation of Host Intestinal Microbiota by Polyphenols in the Development and Prevention of Chronic Kidney Disease

“…Additionally, the expression of nicotinamide adenine dinucleotide phosphate oxidase 4, 8-hydroxy-2 ′ -deoxyguanosine, 3-nitrotyrosine, collagen IV, and fibronectin were decreased, while the expression of endothelial nitric oxide synthase and superoxide dismutase 2 were increased following resveratrol treatment. Resveratrol can thus have protective effects on aging kidneys, via Ang II inhibition, and MasR activation leading to decreased oxidative stress, inflammation, and fibrosis (94).…”

Resveratrol and the Interaction between Gut Microbiota and Arterial Remodelling

“…Moreover, resveratrol can normalize the ACE, Ang I and II, AT2R, and MasR expression through restoring the expression of SIRT1 in high fat diet (HFD)-fed mice [66] and HFD-fed rats [67]. Therefore, the beneficial effects of resveratrol in neointima formation could be mediated by SIRT1, renin-angiotensin-aldosterone system (RAAS) and NF-κB signalling [68].…”