Abstract 236: Intrauterine Growth Restriction Programs A Reduction In Nitric Oxide Bioavailability Indicative Of Accelerated Vascular Aging In The Male Growth-restricted Rat.

Intrauterine growth restriction (IUGR) programs hypertension and endothelial dysfunction at 4 months of age in male IUGR rat offspring compared to male control. Male IUGR offspring at 4 months of age exhibit a significant decrease in the blood pressure (BP) response to chronic NG-nitro-L-arginine methyl ester (L-NAME, 10mg/kg/day) compared to age-matched male control. Albuminuria is also significantly reduced in L-NAME treated male IUGR relative to L-NAME treated male control suggesting that IUGR programs a reduction in bioavailability of nitric oxide (NO). Decreased NO bioavailability by endothelial dysfunction can contribute to increased BP. Age is a risk factor for hypertension and aging is associated with an increase in arterial stiffening and endothelial dysfunction. BP is similar in male IUGR relative to male control by 18 months of age. Thus, this study tested the hypothesis that age-induced reductions in NO bioavailability in the male control rat would abolish the IUGR-induced differential BP and albuminuria response to chronic L-NAME observed in male IUGR rats in young adulthood. To test this hypothesis male control and IUGR rats were treated with L-NAME or vehicle at 18 months of age. Animals underwent weekly 24 hour metabolic studies initiated prior to and during chronic L-NAME; BP was measured in conscious, chronically instrumented animals. As previously observed BP did not differ in untreated male control versus untreated male IUGR (151±4 vs. 153±4 mmHg); however, BP did not differ following chronic treatment with L-NAME in male control versus male IUGR (188±5 vs. 196±9 mmHg); control vs. IUGR, respectively. Thus, age attenuated the differential BP response to chronic L-NAME. Albumin excretion did not differ in male control versus male IUGR prior to initiation of L-NAME (81±11 vs. 96±27 mg/day) or following chronic treatment with L-NAME (127±26 vs. 107±24 mg/day); control vs. IUGR, respectively. Thus, these data suggest that IUGR programs a reduction in NO bioavailability in young adulthood implicating that IUGR programs accelerated vascular aging. Additional studies are needed to understand mechanism and facilitate the development of preventative measures against the intrauterine programming of cardiovascular risk.