Renoprotective effect of azelnidipine in rats.
To assess whether azelnidipine (AZN) exerts renoprotective effects, 20-week-old adult male stroke-prone spontaneously hypertensive rats (SHRsp) were treated with AZN 10 mg/kg/d (n=6), olmesartan (OLM) 3 mg/kg/d (n=4), hydralazine (HYD) 20 mg/kg/d (n=3), or water (control; n=5). Each test agent was administered by oral gavage for 12 weeks. Systolic blood pressure (SBP) was measured every 2 weeks and urinary protein excretion (UproV) every 3 weeks. At the age of 32 weeks, the rats were sacrificed and blood and kidneys collected for biochemical, histological, and immunohistochemical studies. All drug treatments significantly (p<0.05) reduced SBP, UproV, and blood biochemical parameters such as creatinine, total cholesterol, and blood urea nitrogen. Masson trichrome staining and immunohistochemical staining revealed significant (p<0.05) reductions of interstitial fibrosis, collagen type III, nicotinamide-adenine dinucleotide/nicotinamide-adenine dinucleotide phosphate oxidase, and p22(phox) and p47(phox) components expression in the AZN- and OLM-treated groups in comparison with rats treated with HYD and control animals. ED1, 4-hydroxy-2-nonenal (4-HNE), and heat shock protein (HSP)-47 expression was also reduced in the AZN- and OLM-treated groups versus in HYD and control animals. These results indicate that not only OLM but also AZN exerts renoprotective effects through inhibition of macrophage infiltration and antioxidant activity in SHRsp model of renal injury.
Kurashige
Tomomi
T
Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Abe
Katsushige
K
Furusu
Akira
A
Miyazaki
Masanobu
M
Obata
Yoko
Y
Xia
Zihyin
Z
Nakazawa
Masayuki
M
Nakazawa
Yuka
Y
Funakoshi
Satoshi
S
Harada
Takashi
T
Koji
Takehiko
T
Kohno
Shigeru
S
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001806:Blood Urea Nitrogen; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D024061:Collagen Type III / Q000096:biosynthesis; D003627:Data Interpretation, Statistical; D004095:Dihydropyridines / Q000494:pharmacology*; D050958:HSP47 Heat-Shock Proteins / Q000096:biosynthesis; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007677:Kidney Function Tests; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019255:NADPH Oxidases / Q000096:biosynthesis / Q000235:genetics; D010751:Phosphopyruvate Hydratase / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D024061:Collagen Type III; D004095:Dihydropyridines; D050958:HSP47 Heat-Shock Proteins; D001383:Azetidinecarboxylic Acid; D019255:NADPH Oxidases; C515768:Cyba protein, rat; D010751:Phosphopyruvate Hydratase; C061679:azelnidipine