Aldehyde induced hypertension in rats: prevention by N-acetyl cysteine.
Methylglyoxal, a highly reactive endogenous aldehyde is formed in the tissue of humans and animals as an intermediate of glucose and fructose metabolism. N-acetyl cysteine (NAC), an analogue of the dietary amino acid cysteine, binds aldehydes thus preventing their damaging effect on physiological proteins. We measured systolic blood pressure (SBP), platelet [Ca2+]i, circulating nitric oxide levels, tissue aldehyde conjugates and renal vascular changes in chronic methyglyoxal treated Wistar-Kyoto (WKY) rats and examined the effect of NAC in the diet on these parameters. Animals, age seven weeks, were divided into three groups of six animals each and were treated as follows: WKY-control (chow diet and normal drinking water); WKY-methylglyoxal (chow diet and methyglyoxal in drinking water); WKY-methyglyoxal + NAC (1.5% NAC in diet and methylglyoxal in drinking water) for the next 18 weeks. Methylgyoxal in drinking water was given at a concentration of 0.2% during weeks 0-5; 0.4%, weeks 6-10; and 0.8%, weeks 11-18. After 18 weeks systolic blood pressure, platelet [Ca2+]i and kidney aldehyde conjugates were significantly higher and serum nitric oxide levels lower in methylglyoxal treated rats. Methylglyoxal treated rats also showed smooth muscle cell hyperplasia in the small artery and arterioles of the kidney. N-acetyl cysteine, an aldehyde binding thiol compound, prevented these changes.
Vasdev
S
S
Department of Medicine, Memorial University of Newfoundland St. John's, Newfoundland Canada.
Ford
C A
CA
Longerich
L
L
Parai
S
S
Gadag
V
V
Wadhawan
S
S
D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use*; D000447:Aldehydes / Q000032:analysis; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000097:blood; D050260:Carbohydrate Metabolism; D004032:Diet; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D002149:Energy Intake / Q000187:drug effects; D006965:Hyperplasia; D006973:Hypertension / Q000139:chemically induced* / Q000517:prevention & control; D007333:Insulin Resistance; D007668:Kidney / Q000098:blood supply; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D009573:Nitrites / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D011765:Pyruvaldehyde / Q000633:toxicity*; D051381:Rats; D011921:Rats, Inbred WKY; D012077:Renal Artery / Q000187:drug effects / Q000473:pathology; D014781:Viscera / Q000737:chemistry
D000447:Aldehydes; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D011765:Pyruvaldehyde; D002118:Calcium; D000111:Acetylcysteine