Genistein alleviates renin-angiotensin system mediated vascular and kidney alterations in renovascular hypertensive rats

Biomed Pharmacother. 2022 Feb:146:112601. doi: 10.1016/j.biopha.2021.112601. Epub 2022 Jan 4.

Abstract

Genistein is a bioflavonoid mainly found in soybean. This study evaluated the effect of genistein on vascular dysfunction and kidney damage in two-kidney, one-clipped (2K1C) hypertensive rats. Male Sprague-Dawley-2K1C hypertensive rats were treated with genistein (40 or 80 mg/kg) or losartan 10 mg/kg (n = 8/group). Genistein reduced blood pressure, attenuated the increase in sympathetic nerve-mediated contractile response and endothelial dysfunction in the mesenteric vascular beds and aorta of 2K1C rats. Increases in the intensity of tyrosine hydroxylase (TH) in the mesentery and plasma norepinephrine (NE) were alleviated in the genistein-treated group. Genistein also improved renal dysfunction, hypertrophy of the non-clipped kidney (NCK) and atrophy of the clipped kidney (CK) in 2K1C rats. Upregulation of angiotensin II receptor type I (AT1R), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit 4 (Nox4) and Bcl2-associated X protein (BAX) and downregulation of B-cell lymphoma 2 (Bcl2) protein found in CK were restored by genistein. It also suppressed the overexpression of AT1R, transforming growth factor beta I (TGF-β1), smad2/3 and p-smad3 in NCK. Genistein reduced serum angiotensin converting enzyme (ACE) activity and plasma angiotensin II (Ang II) in 2K1C rats. Low levels of catalase activity as well as high levels of superoxide generation and malondialdehyde (MDA) in 2K1C rats were restored by genistein treatment. In conclusion, genistein suppressed renin-angiotensin system-mediated sympathetic activation and oxidative stress in 2K1C rats. It alleviated renal atrophy in CK via modulation of AT1R/NADPH oxidase/Bcl-2/BAX pathways and hypertrophy in NCK via AT1R/TGF-β1/smad-dependent signalling pathways.

Keywords: Genistein; Kidney damage; Oxidative stress; Renin angiotensin system; Renovascular hypertension; Vascular dysfunction.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Disease Models, Animal
  • Genistein / pharmacology*
  • Humans
  • Hypertension, Renovascular / metabolism*
  • Kidney / drug effects*
  • Kidney / pathology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Renin-Angiotensin System / drug effects*

Substances

  • Genistein