Renal-protective effect of nicousamide on hypertensive nephropathy in spontaneously hypertensive rats

Abstract

Previous studies have demonstrated that a novel coumarin-aspirin derivative, nicousamide, has a significant renal-protective effect on diabetic nephropathy. The present study aimed to investigate the beneficial effect of nicousamide on hypertensive nephropathy, as well as the underlying mechanisms in spontaneously hypertensive rats (SHRs). SHRs were treated orally with saline, nicousamide at 15, 30 and 45 mg/kg, and losartan (10 mg/kg) daily for 17 weeks, during which blood pressure (BP) was measured every four weeks. At the end of the 17-week treatment, blood and urine samples were collected for biochemical analysis and kidney tissues were obtained for histopathological and reverse transcription-polymerase chain reaction (RT-PCR) analyses. The concentration of angiotensin (Ang) II in plasma was also examined. Results showed that nicousamide effectively attenuated the progression of hypertensive nephropathy by decreasing urinary albumin excretion (UAE) and blood urea nitrogen (BUN). This could significantly decrease BP (less effectively compared to losartan) and the incidence of glomerulosclerosis and glomerular arteriosclerosis, adequately alleviating tubular impairment. Nicousamide markedly reduced the plasma Ang II level in SHRs and reduced mRNA expression of angiotensin-converting enzyme (ACE) and chymase in the kidneys of SHRs. Thus, nicousamide may retard the progression of hypertensive nephropathy. Although the underlying mechanisms have yet to be fully elucidated, this may involve blocking of the renin-Ang system.