212. Effects of prenatal sildenafil treatment on long-term cardiovascular function in offspring from dahl salt-sensitive rats

Abstract

Introduction Fetal growth restriction (FGR) is associated with increased risk for cardiovascular disorders in later life. Cardiovascular disease is the most common cause of death worldwide. Previous studies report that prenatal sildenafil improves pregnancy outcomes, such as birthweight, in FGR animal models; however, whether sildenafil treatment is protective against long-term cardiovascular disease in these offspring is unknown. Objective We hypothesize that prenatal sildenafil reduces blood pressure and endothelial dysfunction in FGR offspring from Dahl salt-sensitive (SS) rats on normal salt intake. Methods Sildenafil citrate (60 mg/kg/day) or control gel diet was administered from gestational day 10 until birth. Birthweight and litter size were measured (treated n = 10; untreated n = 8 dams). Telemetry devices (DSI) were implanted via the femoral artery to measure mean arterial pressure (MAP) from weeks 5–8 in the offspring (treated n = 12; untreated n = 4). Aortic rings were isolated from 10 week old offspring to assess vascular sensitivity ( logEC 50 ) to endothelial-dependent (acetylcholine) and -independent (sodium nitroprusside, SNP) vasorelaxation (treated n = 10; untreated n = 10). Data shown as mean ± S.E.M. Results No sex differences were observed in any variables; therefore, data were pooled between males and females. Sildenafil improved birthweight (treated 6.8 ± 0.2; untreated 6.2 ± 0.1 g; p = 0.02) without significantly changing viable litter size (treated 9.6 ± 0.9; untreated 7.9 ± 1.0; p = 0.23). While MAP at 5 weeks was similar between groups (treated 107 ± 1; untreated 108 ± 2 mmHg; p = 0.55), there was a trend towards lower MAP in prenatally treated offspring at 8 weeks (treated 116 ± 1; untreated 120 ± 2 mmHg; p = 0.09). Aortas from offspring of treated dams displayed enhanced sensitivity to acetylcholine ( logEC 50 : treated −7.4 ± 0.3; untreated −6.6 ± 0.3 M; p = 0.03), but not to SNP (treated −8.2 ± 0.3; untreated −7.9 ± 0.2 M; p = 0.43). Discussion Prenatal sildenafil treatment improves birthweight in a model of FGR. In young adult offspring, there was a trend towards a sex-independent lowering of blood pressure and increased endothelium-dependent relaxation.