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

Zhang,Sen; Li,Yan; Li,Hongyan; Zheng,Xuguang; Chen,Xiaoguang

doi:10.3892/br.2012.11

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

Authors:
- Sen Zhang
- Yan Li
- Hongyan Li
- Xuguang Zheng
- Xiaoguang Chen
View Affiliations

Affiliations: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China
Published online on: September 25, 2012 https://doi.org/10.3892/br.2012.11
Pages: 34-40

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

1.	Azegami T, Sasamura H, Hayashi K and Itoh H: Vaccination against the angiotensin type 1 receptor for the prevention of L-NAME-induced nephropathy. Hypertens Res. 35:492–499. 2012. View Article : Google Scholar : PubMed/NCBI
2.	Hill GS: Hypertensive nephrosclerosis. Curr Opin Nephrol Hypertens. 17:266–270. 2008. View Article : Google Scholar
3.	Chen Y, Lipkowitz MS, Salem RM, et al: Progression of chronic kidney disease: adrenergic genetic influence on glomerular filtration rate decline in hypertensive nephrosclerosis. Am J Nephrol. 32:23–30. 2010. View Article : Google Scholar : PubMed/NCBI
4.	Wang G, Lai FM, Kwan BC, et al: Expression of ACE and ACE2 in patients with hypertensive nephrosclerosis. Kidney Blood Press Res. 34:141–149. 2011. View Article : Google Scholar : PubMed/NCBI
5.	Zhang H, Jin J, Zhou W, et al: Nicousamide, a potent inhibitor of phosphorylation by TGF-β receptor II. Acta Pharmaceutica Sinica. 1:160–165. 2011.
6.	Li H, Zheng X, Wang H, Zhang Y, Xin H and Chen X: XLF-III-43, a novel coumarin-aspirin compound, prevents diabetic nephropathy in rats via inhibiting advanced glycation end products. Eur J Pharmacol. 627:340–347. 2010. View Article : Google Scholar : PubMed/NCBI
7.	Li H, Zhang Y, Wang H, Zheng X and Chen X: Nicousamide blocks the effects of advanced glycation end products on renal cells. Eur J Pharmacol. 674:455–459. 2012. View Article : Google Scholar : PubMed/NCBI
8.	Sheng L, Chen H and Li Y: A HPLC method for determination of nicousamide in dog plasma and its application to pharmaco-kinetic studies. J Chromatogr B Analyt Technol Biomed Life Sci. 854:99–103. 2007. View Article : Google Scholar : PubMed/NCBI
9.	Jakus V and Rietbrock N: Advanced glycation end-products and the progress of diabetic vascular complications. Physiol Res. 53:131–142. 2004.PubMed/NCBI
10.	Wendt TM, Tanji N, Guo J, et al: RAGE drives the development of glomerulosclerosis and implicates podocyte activation in the pathogenesis of diabetic nephropathy. Am J Pathol. 162:1123–1137. 2003. View Article : Google Scholar : PubMed/NCBI
11.	Tian D, Ling S, Chen G, et al: Hypertensive nephropathy treatment by heart-protecting musk pill: a study of anti-inflammatory therapy for target organ damage of hypertension. Int J Gen Med. 4:131–139. 2011.PubMed/NCBI
12.	Sun L, Ke Y, Zhu CY, et al: Inflammatory reaction versus endogenous peroxisome proliferator-activated receptors expression, re-exploring secondary organ complications of spontaneously hypertensive rats. Chin Med J (Engl). 121:2305–2311. 2008.
13.	Koshikawa S, Nishikimi T, Inaba C, Akimoto K and Matsuoka H: Fasudil, a Rho-kinase inhibitor, reverses L-NAME exacerbated severe nephrosclerosis in spontaneously hypertensive rats. J Hypertens. 26:1837–1848. 2008. View Article : Google Scholar : PubMed/NCBI
14.	Alfie J, Aparicio LS and Waisman GD: Current strategies to achieve further cardiac and renal protection through enhanced renin-angiotensin-aldosterone system inhibition. Rev Recent Clin Trials. 6:134–146. 2011. View Article : Google Scholar
15.	Berl T: Review: renal protection by inhibition of the renin-angiotensin-aldosterone system. J Renin Angiotensin Aldosterone Syst. 10:1–8. 2009. View Article : Google Scholar : PubMed/NCBI
16.	Susic D, Frohlich ED, Kobori H, Shao W, Seth D and Navar LG: Salt-induced renal injury in SHRs is mediated by AT1 receptor activation. J Hypertens. 29:716–723. 2011. View Article : Google Scholar : PubMed/NCBI
17.	Varagic J, Ahmad S, Brosnihan KB, et al: Salt-induced renal injury in spontaneously hypertensive rats: effects of nebivolol. Am J Nephrol. 32:557–566. 2010. View Article : Google Scholar : PubMed/NCBI
18.	Ehara T and Shigematsu H: Mast cells in the kidney. Nephrology (Carlton). 8:130–138. 2003. View Article : Google Scholar : PubMed/NCBI
19.	Jones C: Matrix degradation in renal disease. Nephrology (Carlton). 2:13–23. 1996. View Article : Google Scholar
20.	Siragy HM: Angiotensin II compartmentalization within the kidney: effects of salt diet and blood pressure alterations. Curr Opin Nephrol Hypertens. 15:50–53. 2006. View Article : Google Scholar : PubMed/NCBI