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 Nω‐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.