Aerobic training restores endothelial function in intrauterine growth restricted rats: Possible involvement of eNOSThr495 phosphorylation

Abstract

PurposeTo evaluate the effects of aerobic training on vascular reactivity in adult male offspring submitted to intrauterine growth restriction.MethodsProcedures approved by Ethics Committee of UNIFESP (836880). Pregnant Wistar Rats were submitted to Ad libitum or 50% of Ad libitum diet throughout gestation. At birth, pups were weighted. Adult Male offspring of both groups were assigned to Sedentary Control (SC), Sedentary Restricted (SR), Trained Control (TC) and Trained Restricted (TR). After AT (10 weeks, 5 days/week, 1h/day, 50–60% of maximum exercise capacity) femoral artery was cannulated to register mean arterial blood pressure (BP) and heart rate (HR). The vasodilatation endothelium‐dependent and endothelium‐independent were assessed by concentration‐response curves to Acetylcholine (ACh:10–9M‐3X10‐5M) and Sodium Nitroprusside (SNP:10‐9M‐10‐6M), respectively in thoracic aorta rings. In addition, we evaluated in thoracic aorta: protein expression of total eNOS, p‐eNOSSer1177, and p‐eNOSThr495 using western blotting, and nitric oxide concentration by NO analyzer. Results are shown as mean ± EPM, test t de student or Two‐way ANOVA following Bonferroni were used.ResultsIUGR was confirmed by birth weight (Control:7.01±0.34g vs. Restricted:4.3±0.08g). AT‐restored BP in TR (SC:118±3mmHg; TC:110±2 mmHg; SR:129±2 mmHg; TR:110±4 mmHg) and lead to a reduction in HR (SC:355±13bpm; TC:321±4 bpm; SR:343±4 bpm; TR:309±7 bpm). AT normalized the relaxation to ACh (SC:92.18±2.7%; TC:90.05±2.04%; SR:65.04±4.4%; TR:93.35±1.7%) in aorta from IUGR rats, whereas vasodilatation to SNP was not altered (SC:98.45±2.38%; TC:97.84±1.68%; SR:93.97±2.64%; TR:97.64±0.90%). p‐eNOS Ser1177 expression was similar among groups (data not show). However, AT‐reduced the increased p‐eNOSThr495 found in aorta from RT group (SC:0.53±0.03; TC:0.51±0.10; SR:0.86±0.06; TR: 0.59±0.04). Nitric oxide concentration was increased in RT (SC: 426.2±63.03μM/mg; TC: 349±46 μM/mg; SR: 217.8±18.22 μM/mg; TR: 355±53 μM/mg).ConclusionOur results indicated that AT‐restores endothelial function in intrauterine growth restricted rats, in part due to reduction in p‐eNOSThr495 expression associated to increase in nitric oxide concentration in thoracic aorta.Support or Funding InformationFAPESP: 2013/00311‐6