Carbonyl stress induces hypertension and cardio-renal vascular injury in Dahl salt-sensitive rats.
One major precursor of carbonyl stress, methylglyoxal (MG), is elevated in the plasma of chronic kidney disease (CKD) patients, and this precursor contributes to the progression of vascular injury, hypertension and renal injury in diabetic nephropathy patients. This molecule induces salt-sensitive hypertension via a reactive oxygen species-mediated pathway. We examined the role of MG in the pathogenesis of hypertension and cardio-renal injury in Dahl salt-sensitive (Dahl S) rats, which is a rat model of CKD. Nine-week-old Dahl S rats were fed a 1% NaCl diet, and 1% MG was added to their drinking water for up to 12 weeks. Blood pressure and cardio-renal injuries were compared with rats treated with tap water alone. The angiotensin II receptor blocker (ARB), candesartan (10 mg kg(-1) day(-1)), was administered to MG Dahl S rats to determine the impact of this drug on the pathogenesis of MG-induced CKD. A progressive increase in systolic blood pressure was observed (123±1-148±5 mm Hg) after 12 weeks of MG administration. MG administration significantly increased urinary albumin excretion, glomerular sclerosis, tubular injury, myocardial collagen content and cardiac perivascular fibrosis. MG also enhanced the renal expression of Nɛ-carboxyethyl-lysine (an advanced glycation end product), 8-hydroxydeoxyguanosine (a marker of oxidative stress), macrophage (ED-1) positive cells (a marker of inflammation) and nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase activity. Candesartan treatment for 4 weeks significantly reduced these parameters. These results suggest that MG-induced hypertension and cardio-renal injury and increased inflammation and carbonyl and oxidative stress, which were partially preventable by an ARB.
Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Xianguang
X
Chen
Takefumi
T
Mori
Qi
Q
Guo
Chunyan
C
Hu
Yusuke
Y
Ohsaki
Yoshimi
Y
Yoneki
Wanjun
W
Zhu
Yue
Y
Jiang
Satoshi
S
Endo
Keisuke
K
Nakayama
Susumu
S
Ogawa
Masaaki
M
Nakayama
Toshio
T
Miyata
Sadayoshi
S
Ito
D000419:Albuminuria / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000502:physiology; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D005355:Fibrosis / Q000473:pathology; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects / Q000502:physiology*; D011765:Pyruvaldehyde / Q000097:blood; D051381:Rats; D020303:Rats, Inbred Dahl; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000187:drug effects; D017673:Sodium Chloride, Dietary / Q000009:adverse effects; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000627:therapeutic use
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D017673:Sodium Chloride, Dietary; D013777:Tetrazoles; D011765:Pyruvaldehyde; D019255:NADPH Oxidases; C081643:candesartan