Age impacts the developmental programming of blood pressure regulation in the intrauterine growth‐restricted male rat (1085.10)

Abstract

Age impacts the developmental programming of blood pressure regulation in the intrauterine growth restricted male rat John Henry Dasinger, Sattira Intapad, Miles A. Backstrom, Barbara T. Alexander. Department of Physiology University of Mississippi Medical Center, Jackson MS, 39216 Intrauterine growth restriction (IUGR) induced by placental insufficiency programs hypertension, enhanced blood pressure (BP) response to acute angiotensin II (Ang II) and a two‐fold increase in circulating testosterone (T) at 4 months of age versus male control. Hypertension and the enhanced pressor response to acute Ang II at 4 months of age were abolished by castration implicating that programming of cardiovascular risk is T‐dependent. T levels decrease with age in men. We recently demonstrated that plasma T also decreases with age in male IUGR resulting in normalizing of circulating T levels relative to male control by one year of age. Thus, we tested the hypothesis that the age‐related reduction in circulating T in male IUGR rats would normalize BP and attenuate hyperresponsiveness to acute Ang II relative to age‐matched male controls. BP and Ang II sensitivity were measured in conscious, chronically catheterized male rats plus or minus Ang II (100ng‐kg‐1‐min‐1 for 20 minutes) at one year of age. BP in untreated animals was not significantly elevated in male IUGR (131±5 mmHg) relative control (123±3 mmHg). The enhanced pressor response to acute Ang II was not observed in male IUGR relative to control (IUGR vs. Control, Δ17 vs. Δ18 mmHg). Thus, these data indicate that developmental programming of hypertension and enhanced Ang II sensitivity is lost with the age‐related reduction in circulating T in male IUGR rats.Grant Funding Source: Supported by HL074927, HL51971, 12POST11980021