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437 Sildenafil does not attenuate the expected cardiac changes in hypertensive rats Fernand D. Samson, Laura G. Willingham, Naiha Mussarat, Giancarlo Mari, Mauro Schenone, Danielle L. Tate University of Tennessee Health Science Center, Memphis, TN OBJECTIVE:Women with a history of preeclampsia are at an increased risk of developing premature cardiovascular disease due to endothelial dysfunction. Faulty cyclic guanosine3’,5’-monophosphate (cGMP) signaling secondary to the upregulation of phosphodiesterase (PDE) isoenzymes is seen in both cardiovascular disease and preeclampsia. We hypothesize that sildenafil, a PDE5 inhibitor, may attenuate the expected cardiac changes associated with the selective reduced uterine perfusion pressure (SRUPP) rat model of hypertensive disorders in pregnancy STUDY DESIGN: Pregnant Sprague-Dawley rats were divided into one of 4 groups: sham (n1⁄412), SRUPP (n1⁄412), sham with sildenafil (sham+S) (n1⁄410), and SRUPP with sildenafil (SRUPP+S) (n1⁄411). On gestational day (GD) 13 the rats underwent maternal echocardiography. On GD 14, rats were anesthetized with 2% isoflurane and the abdomen entered through a midline vertical incision. Uterine and utero-ovarian arteries were identified and surgically isolated. In the SRUPP and SRUPP+S groups, silver clips (0.102mm internal diameter) were placed on the aforementioned vessels bilaterally. The sham and sham+S groups’ vessels were solely isolated. The rats were returned to their home cages after surgery. From GD14 to GD20 the SRUPP+S and sham+S groups were fed 20g/day of rat chow with sildenafil at an inclusion rate of 625mg/kg diet with the goal to deliver 50mg/kg/day (sildenafil 12.5mg/d). The remaining groups were given 20g of similar rat chow without sildenafil. On GD 20, all pregnant rats underwent repeat maternal echocardiography. Analysis of Variance (ANOVA) with post hoc multiple comparison tests were used to analyze data. A p value of <0.05 determined statistical significance. RESULTS: There was no significant difference in echocardiogram parameters among the groups on GD 13. On GD 20, the cardiac output (CO) in the SRUPP group (64.63 + 2.03 mL/min) was significantly increased compared to the sham surgery group (49.35 + 3.58 mL/min)(p1⁄4 0.008). Additionally, the stroke volume differed significantly between the SRUPP surgery group (166.29 + 6.19uL) and the sham surgery group (135.20 + 9.35 uL)(p1⁄40.047). The CO was increased in the SRUPP+S group (77.73 + 16.4 mL/min) when compared to the SRUPP group (64.63 + 2.02), however this was not statistically significant(p1⁄4 0.07). CONCLUSION: Sildenafil does not attenuate the expected changes in cardiac function associated with hypertensive disorders of pregnancy as seen in the SRUPP rat model.