title: Renin angiotensin system blockade ameliorates lead nephropathy.
abstract: Lead intoxication is usually insidious and may cause a variety of complications such as kidney damage and hypertension. The role of intrarenal renin-angiotensin system (RAS) in lead-induced nephropathy has not been investigated. Adult male Sprague-Dawley rats were fed with water containing 250ppm of lead acetate (lead group) and deionized water (control group) for 4weeks. Another two groups started to receive intraperitoneal captopril (50mg/kg/d) or losartan (10mg/kg/d) after 2weeks of lead feeding and continued for another 2weeks. Immunoblotting was used to analyze the protein amount of intrarenal RAS components and transforming growth factor-beta (TGF-β). Compared with control group, lead exposure resulted in increased proteinuria after 2-week treatment (4.2±0.9mg/100g vs. 1.8±0.8mg/100g, p<0.05) and 4-week (5.2±1.7mg/100g, p<0.05). Serum creatinine level was increased (0.40±0.2 vs. 0.3 ±.04mg/dL, p<0.05) and calculated glomerular filtration rate (GFR) was decreased (2.68±1.03 vs. 3.37±0.11mL/min, p<0.05). Intrarenal angiotensin converting enzyme (ACE), angiotensin II (ANG II), angiotensin II type 1 receptor (AT1R) and transforming growth factor-beta (TGF-β) were upregulated in lead group. Captopril and losartan administration reduced proteinuria significantly (3.0±0.50mg/100g of captopril and 2.7±0.4mg/100g of losartan group) and lowered systolic blood pressure when compared with lead group. Furthermore, serum creatinine levels and GFR were improved by RAS blockade. Captopril treatment significantly reduced protein abundance of ACE, ANG II, AT1R and TGF-β. Losartan treatment also decreased ANG II and TGF-β. We concluded that lead exposure elicited intrarenal RAS activation with associated proteinuria and impaired renal function. RAS blockade was effective in alleviating lead-associated kidney injury and lowering blood pressure.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Hwee-Yeong
authors.initials: HY
authors.lastname: Ng
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Tain
authors.forename: Yueh-Ting
authors.initials: YT
authors.lastname: Lee
authors.forename: Chung-Yao
authors.initials: CY
authors.lastname: Hsu
authors.forename: Terry Ting-Yu
authors.initials: TT
authors.lastname: Chiou
authors.forename: Pei-Chen
authors.initials: PC
authors.lastname: Huang
authors.forename: Chien-Te
authors.initials: CT
authors.lastname: Lee
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D002216:Captopril / Q000494:pharmacology; D005786:Gene Expression Regulation; D005919:Glomerular Filtration Rate; D007674:Kidney Diseases / Q000139:chemically induced*; D007855:Lead Poisoning / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D019808:Losartan
keywords: Lead; Renal injury; Renin-angiotensin system