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Involvement of the Endothelial Nitric Oxide Pathway and Leukocyte Infiltration in Secondhand Smoke Exposure‐Induced Vascular Endothelial Dysfunction and Hypertension
Author(s) -
El-Mahdy Mohamed A,
Abdelghany Tamer M,
Hemann Craig,
Varadharaj Saradhadevi,
Esmat Ahmed,
El-Sherbiny Gamal A,
Zweier Jay L
Publication year - 2012
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.26.1_supplement.866.7
Subject(s) - enos , endothelial dysfunction , nitric oxide , nad(p)h oxidase , medicine , nadph oxidase , endothelium , endocrinology , nitric oxide synthase , chemistry , oxidative stress
Loss of nitric oxide (NO) production due to dysfunction of endothelial NO synthase (eNOS) occurs in a wide range of cardiovascular disease and has been linked to secondhand smoke (SHS)‐induced vascular endothelial dysfunction (VED). Our aim was to investigate the mechanisms of SHS‐induced VED. C57BL/6 mice were exposed for up to 48 weeks to SHS generated from 3R4F reference research cigarettes using the Teague smoking machine. SHS‐exposed (SHSE) mice showed persistent hypertension and impairment of acetylcholine‐induced endothelium‐dependent relaxation of thoracic aorta. Expression of NAD(P)H oxidase subunits p22 phox and gp91 phox increased in aortas of SHSE mice with concomitant superoxide production. H&E stained aortic sections showed evidence of leukocyte infiltration in SHSE mice. Plasma of SHSE mice showed significant depletion of tetrahydrobiopterin (BH 4 ). Western blotting and immunohistochemistry showed a decrease in eNOS expression in SHSE mice aortas. Also, phosphorylation of eNOS and Aktwas decreased in SHSE mice. In conclusion, SHS induces leukocyte infiltration that triggers NAD(P)H oxidase over‐expression and ROS generation which leads to depletion of BH 4 and eNOS uncoupling, resulting in VED and hypertension. Overall, our study provides important insights toward understanding contributions of SHS exposure to the genesis of cardiovascular disease. (NIH # HL38324 to JLZ)