Prenatal cocaine exposure causes sex-dependent impairment in the myogenic reactivity of coronary arteries in adult offspring.
Cocaine abuse is a significant problem among pregnant women. The present study tested the hypothesis that prenatal cocaine exposure impairs myogenic reactivity of coronary arteries in adult offspring. Pregnant rats received cocaine (30 mg kg(-1) day(-1)) or saline from days 15 to 21 of gestational age, and experiments were conducted in 3-month-old offspring. In pressurized coronary septal arteries, the diameter and vessel wall intracellular Ca2+ concentrations were measured simultaneously in the same tissue as a function of intraluminal pressure. Cocaine did not affect KCl-induced contractions of coronary arteries in either males or females but decreased the distensibility in male vessels. In male offspring, cocaine treatment resulted in a significant decrease in pressure-dependent myogenic contractions. Inhibition of eNOS with NG-nitro-L-arginine did not alter the myogenic response in either saline control or cocaine-treated animals. In females, cocaine caused a significant increase in pressure-dependent myogenic contractions. NG-nitro-L-arginine did not affect the myogenic response in the control animals but blocked the cocaine-mediated effect. In both males and females, the pressure-induced increases in vessel wall Ca2+ concentrations were not significantly different between cocaine and saline groups. The ratio of changes in the diameter to Ca2+ concentrations in the pressurized arteries was significantly less in male but greater in female offspring after cocaine treatment. The results suggest that prenatal cocaine exposure causes reprogramming of coronary myogenic tone via changes in the Ca2+ sensitivity in a sex-dependent manner, leading to an increased risk of dysfunction of coronary autoregulation in adult offspring.
Xiao
DaLiao
D
Center for Perinatal Biology, Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Yang
Shumei
S
Zhang
Lubo
L
D000818:Animals; D003042:Cocaine / Q000633:toxicity*; D019970:Cocaine-Related Disorders; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000503:physiopathology; D011247:Pregnancy; D011248:Pregnancy Complications; D011297:Prenatal Exposure Delayed Effects; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012737:Sex Factors; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D003042:Cocaine
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