Vascular effects of aerobic exercise training in rat adult offspring exposed to hypoxia-induced intrauterine growth restriction.

KEY POINTS: Prenatal hypoxia, one of the most common consequences of complicated pregnancies, leads to intrauterine growth restriction (IUGR) and impairs later-life endothelium-dependent vascular function. Early interventions are needed to ultimately reduce later-life risk for cardiovascular disease. Aerobic exercise training has been shown to prevent cardiovascular diseases. Whether exercise can be used as an intervention to reverse the vascular phenotype of this susceptible population is unknown. Aerobic exercise training enhanced endothelium-derived hyperpolarization-mediated vasodilatation in gastrocnemius muscle arteries in male IUGR offspring, and did not improve nitric oxide-mediated vasodilatation in IUGR offspring. Understanding the mechanisms by which exercise impacts the cardiovascular system in a susceptible population and the consideration of sexual dimorphism is essential to define whether exercise could be used as a preventive strategy in this population. ABSTRACT: Hypoxia in utero is a critical insult causing intrauterine growth restriction (IUGR). Adult offspring born with hypoxia-induced IUGR have impaired endothelium-dependent vascular function. We tested whether aerobic exercise improves IUGR-induced endothelial dysfunction. Pregnant Sprague-Dawley rats were exposed to control (21% oxygen) or hypoxic (11% oxygen) conditions from gestational day 15 to 21. Male and female offspring from normoxic and hypoxic (IUGR) pregnancies were randomized at 10 weeks of age to either an exercise-trained or sedentary group. Exercise-trained rats ran on a treadmill for 30 min at 20 m min(-1) , 5 deg gradient, 5 days week(-1) , for 6 weeks. Concentration-response curves to phenylephrine and methylcholine were performed in second order mesenteric and gastrocnemius muscle arteries, in the presence or absence of l-NAME (100 μm), MnTBAP (peroxynitrite scavenger; 10 μm), apamin (0.1 μm) and TRAM-34 (an intermediate-conductance calcium-activated potassium channel blocker; 10 μm), or indomethacin (5 μm). In adult male IUGR offspring, prenatal hypoxia had no effect on total vasodilator responses in either vascular bed. Aerobic exercise training in IUGR males, however, improved endothelium-derived hyperpolarization (EDH)-mediated vasodilatation in gastrocnemius muscle arteries. Female IUGR offspring had reduced NO-mediated vasodilatation in both vascular beds, along with decreased total vasodilator responses and increased prostaglandin-mediated vasoconstriction in gastrocnemius muscle arteries. In contrast to males, aerobic exercise training in IUGR female offspring had no effect on either vascular bed. Exercise may not prove to be a beneficial therapy for specific vascular pathways affected by prenatal hypoxia, particularly in female offspring.