Mechanism of acrolein-induced vascular toxicity.
Acrolein, an environmental pollutant and a lipid peroxidation product, is implicated in vascular pathogenesis. Although evidence indicates a link between vascular pathogenesis and acrolein, no direct studies relating to effects of acrolein on vascular function and responses are known. This study investigated the effects of acrolein on vascular function to understand the underlying mechanism of acrolein-induced vascular responses. Male Sprague-Dawley rats were treated with acrolein (2 or 4 mg/kg; i.p.) for 3 or 7 days. Urine and blood samples were collected. Changes in systolic blood pressure (SBP) and responses to acetylcholine and phenylephrine were determined. Acrolein (4 mg/kg, 7 days) significantly increased SBP by 25%, phenylephrine vasoconstriction by 2-fold, but decreased urinary excretion of nitrite by 25%. Acrolein inhibited generation of cyclic guanosine 3'5'-monophosphate (cGMP) by 98%, and did not alter expression of nitric oxide synthase (eNOS). Acrolein increased the generation of lipid hydroperoxide in plasma and aortic tissue by 21% and 124% respectively, increased glutathione-S-transferase (GST) and glutathione peroxidase (GSH-Px) activities. Acrolein up-regulated the expression of GST by 2 fold. These data suggest that induced SBP and altered vasoconstriction/vasodilatation in acrolein treated rats may be due to reduced availability of NO via increased free radical generation and reduced antioxidant defense.
Yousefipour
Z
Z
College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA. yousefipour_zx@tsu.edu
Ranganna
K
K
Newaz
M A
MA
Milton
S G
SG
D000171:Acrolein / Q000633:toxicity*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D015153:Blotting, Western; D006152:Cyclic GMP / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014652:Vascular Diseases / Q000139:chemically induced* / Q000473:pathology*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D004785:Environmental Pollutants; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D000171:Acrolein; D005979:Glutathione Peroxidase; D019001:Nitric Oxide Synthase; D005982:Glutathione Transferase; D006152:Cyclic GMP