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Chronic Exposure to Polychlorinated Biphenyls Alters Vascular Relaxation and Cerebral Microvascular eNOS Expression
Author(s) -
Ngala Yaje M,
Anozie Ogechukwu,
Nsaif Rami H,
Sapp John B,
Oyekan Adebayo A,
Yakubu Momoh A.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a642
Subject(s) - enos , phenylephrine , medicine , endocrinology , acetylcholine , vascular smooth muscle , bradykinin , endothelial dysfunction , chemistry , oxidative stress , vasodilation , endothelium , nitric oxide , blood pressure , nitric oxide synthase , smooth muscle , receptor
Polychlorinated Biphenyls (PCBs) are environmental pollutants which enter the biological system through food products. Accumulation of PCBs has been reported to cause developmental delays, motor dysfunction, cardiovascular disorders and diabetes. We tested the hypothesis that chronic PCBs accumulation induces vascular dysfunction by a mechanism involving PKC. Rats were treated with PCBs (100 or 300 μmol/kg) for 1, 4, or 8 wks. Effects of chronic PCBs on vascular reactivity to acetylcholine (ACh, 10 −9 –10 −4 M) or bradykinin (BK, 10 −9 –10 −4 M) in the aorta and on eNOS and PKC protein expression in cerebral microvessels were determined. ACh or BK dose‐dependently relaxed phenylephrine (PE, 10 −7 M) contracted aortic ring and was attenuated from 56±10% to −3±3% (ACh 10 −5 M) or 50±10% to −14±13% (BK 10 −5 M) in low dose PCB (100 μmol/kg) for 8 wks (p<0.05, n=4; ANOVA). PCBs (300 μmol/kg) for 1 wk had no significant effects on ACh or BK relaxations (56±10% vs. 43±10% or 50±10% vs. 63±6%); however, treatment for 4 wks reduced ACh or BK relaxations to 27±13% or 22±8% (p<0.05, n=4, ANOVA). In cerebral microvessels, eNOS but not PKC expression was significantly increased by acute and reduced by chronic low dose PCBs treatment. These results show that long‐term slow accumulation of PCBs in the body results in vascular dysfunction characterized by loss of endothelium‐dependent relaxation as well as reduction in cerebral microvascular eNOS expression. Thus, chronic low dose exposure to PCBs as in real life scenario can contribute to cardiovascular and possibly to neurological dysfunction through alteration of essential signaling protein. This work was supported by grants from HL03674 and HL70669.