Blockade of the renin angiotensin system abolishes age‐dependent hypertension in female intrauterine growth restricted rats in the absence of an enhanced sensitivity to acute angiotensin II (1085.2)

Abstract

Low birth weight (LBW) as an indicator of poor fetal growth is a risk factor for hypertension. Placental insufficiency induces intrauterine growth restriction (IUGR) in the female rat indicative of LBW. Female IUGR rats exhibit an enhanced sensitivity to acute angiotensin II (Ang II) while remaining normotensive under basal conditions at 4 months of age. Yet, female IUGR rats develop hypertension by 12 month of age. Thus, this study tested the hypothesis that the renin angiotensin system (RAS) contributes to the etiology of age‐dependent hypertension in the female IUGR rat. At 12 months of age rats were treated with vehicle or the ACE inhibitor, enalapril (250 mg/L in drinking water ad libitum), for 2 weeks then mean arterial pressure (MAP) was measured in conscious, chronically instrumented rats. MAP was significantly higher in untreated IUGR versus untreated control rats (134±3 vs. 117±4 mmHg, P<0.05; respectively); enalapril abolished the difference in MAP (118±2 vs. 113±1 mmHg; respectively). Acute infusion (20 min) of Ang II (100 ng/kg/min) increased MAP in all groups (155±3, 164±2, 148±1, 154±2 mmHg; control untreated, IUGR untreated, control treated & IUGR treated; respectively). Yet, the increase in MAP to Ang II was not enhanced in IUGR versus control counterpart. Thus, these data suggest that the RAS contributes to age‐dependent hypertension in the female IUGR in the absence of enhanced sensitivity to Ang II.Grant Funding Source: Supported by HL074927, HL51971, 12POST11980021