Kaempferol Ameliorates Renal Remodelling by Inhibiting the Renin-Angiotensin System Cascade in Hypertensive Rats

Abstract

Background. Kaempferol is a natural flavonoid with a wide range of pharmacological effects. The current study tested whether kaempferol prevents hypertension-induced renal remodelling in rats. During the 5 weeks of experiments, rats (n = 7/group) were administered N_ω-nitro-L-arginine methyl ester hydrochloride (L-NAME) (40 mg/kg/day) with either vehicle or kaempferol (20 mg/kg/day) or kaempferol (40 mg/kg/day) or lisinopril (5 mg/kg/day). Results. Kaempferol treatment alleviated haemodynamic changes occurring in hypertensive rats, including increases in systolic and diastolic blood pressure, pulse pressure, mean arterial pressure, and heart rate (p < 0.05). Kaempferol treatment prevented glomerular hypertrophy by reducing the increased glomerular cross-sectional area, glomerular tuft area, Bowman’s space area, glomerular volume, and the extent of renal tubulointerstitial fibrosis induced by hypertension (p < 0.05). Furthermore, animals in the L-NAME group showed elevated angiotensin-converting enzyme (ACE) activity and angiotensin II (Ang II) levels compared to those in the kaempferol-treated group (p < 0.05). Kaempferol treatment also reverted the elevations in levels of superoxide anions and malondialdehyde and reduced catalase and superoxide dismutase activity in hypertensive rats (p < 0.05). L-NAME-treated rats showed overexpression of angiotensin II receptor type 1 (AT1), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), and matrix metalloproteinase-9 (MMP-9) proteins; conversely, the expression of these proteins was reduced in the kaempferol-treated group (p < 0.05). Conclusion. Kaempferol treatment alleviated renal remodelling induced in rats by chronic hypertension. These mechanisms may be associated with the inhibition of ACE activity and suppression of the Ang II/AT1 receptor/NOX4/MMP-9 cell signalling pathway in renal tissue.