ZHANG Lu-Bo~1,XIAO Da-Liao~1,YANG Shu-Mei~2 1 Center for Perinatal Biology,Department of Physiology and Pharmacology,Loma Linda University School of Medicine,Loma Linda,California 92350,USA;2 Department of Chemistry and Biochemistry,California State University,San Bernardino,California 92407,USA
<正>Cocaine abuse is a significant problem among pregnant women and offspring born to mothers with a history of cocaine abuse have an increased risk of cardiovascular disease.The present study tested the hypothesis that prenatal cocaine exposure increases contractility of resistance arteries in adult male offspring.Pregnant rats received cocaine(30 mg/kg/day)or saline from days 15 to 21 of gestational age.Resistance-sized mesenteric arteries(~150μm)were isolated from 3-month-old male offspring.Arteries were loaded with Fura-2 and pressurized to 45 mmHg in an organ chamber.Cocaine treatment had no significant effect on KCl-induced contractions of the pressurized arteries,but significantly increased norepinephrine-induced contractions.Norepinephrine-stimulated intracellular Ca~(2+) mobilization was the same in the arteries of both saline control and cocaine-treated animlas. However,cocaine treatment significantly increased norepinephrine-mediated Ca~(2+) sensitivity of contractile filaments. Pretreatment of the arteries with endothelial nitric oxide synthase(eNOS)inhibitor N~G-nitro-L-arginine(L-NNA) significantly increased norepinephrine-induced dose-dependent contractions of arteries in control animals but not in the arteries from the offspring treated with cocaine prenatally.Additionally,cocaine treatment significantly de- creased acetylcholine-induced,endothelium-dependent relaxations of mesenteric arteries.The decreased relaxation was associated with decreased intracellular Ca~(2+) concentrations in the arteries.In accordance with the decreased endothelium-dependent relaxation,there was a significant reduction in phospho-eNOS levels in the arteries from cocaine-treated offspring as compared with control animals.The results suggest that prenatal cocaine exposure causes programming of vascular function of resistance arteries in adult male offspring by decreasing endotheliummediated relaxation and increasing arterial contractility,which may lead to an increased risk of hypertension in later life.
programming;;calcium;;nitric oxide;;resistance artery
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