title: Prenatal lipopolysaccharide exposure causes mesenteric vascular dysfunction through the nitric oxide and cyclic guanosine monophosphate pathway in offspring.
abstract: Cardiovascular diseases, such as hypertension, could be programmed in fetal life. Prenatal lipopolysaccharide (LPS) exposure in utero results in increased blood pressure in offspring, but the vascular mechanisms involved are unclear. Pregnant Sprague-Dawley rats were intraperitoneally injected with LPS (0.79mg/kg) or saline (0.5ml) on gestation days 8, 10, and 12. The offspring of LPS-treated dams had higher blood pressure and decreased acetylcholine (ACh)-induced relaxation and increased phenylephrine (PE)-induced contraction in endothelium-intact mesenteric arteries. Endothelium removal significantly enhanced the PE-induced contraction in offspring of control but not LPS-treated dams. The arteries pretreated with l-NAME to inhibit nitric oxide synthase (eNOS) in the endothelium or ODQ to inhibit cGMP production in the vascular smooth muscle had attenuated ACh-induced relaxation but augmented PE-induced contraction to a larger extent in arteries from offspring of control than those from LPS-treated dams. In addition, the endothelium-independent relaxation caused by sodium nitroprusside was also decreased in arteries from offspring of LPS-treated dams. The functional results were accompanied by a reduction in the expressions of eNOS and soluble guanylate cyclase (sGC) and production of NO and cGMP in arteries from offspring of LPS-treated dams. Furthermore, LPS-treated dam's offspring arteries had increased oxidative stress and decreased antioxidant capacity. Three-week treatment with TEMPOL, a reactive oxygen species (ROS) scavenger, normalized the alterations in the levels of ROS, eNOS, and sGC, as well as in the production of NO and cGMP and vascular function in the arteries of the offspring of LPS-treated dams. In conclusion, prenatal LPS exposure programs vascular dysfunction of mesenteric arteries through increased oxidative stress and impaired NO-cGMP signaling pathway.
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China.
authors.forename: Xinquan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China.
authors.forename: Jialiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China.
authors.forename: Caiyu
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Pei
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China.
authors.forename: Jinjuan
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China.
authors.forename: Zaichen
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China. Electronic address: linzhou65@hotmail.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, People's Republic of China; Chongqing Institute of Cardiology, Chongqing, People's Republic of China. Electronic address: chunyuzeng01@163.com.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D005260:Female; D006973:Hypertension / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000276:immunology / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013152:Splanchnic Circulation / Q000276:immunology*; D014664:Vasodilation
chemical_list: D008070:Lipopolysaccharides; D009569:Nitric Oxide; D006152:Cyclic GMP
keywords: Endothelium; Fetal programming; Hypertension; Lipopolysaccharide; Mesenteric artery; Nitric oxide; Oxidative stress; cGMP