A134. Antihypertensive effects of vascular endothelial growth factor 121 on hypertension induced by adenovirus mediated soluble fms-like tyrosine kinase-1 (sFlt-1) gene transfection in rat

Abstract

Soluble fms-like tyrosine kinase-1 (sFlt-1) is receptor of VEGF. Over production of sFlt-1 in pregnant has been considered as the major contributor to the development of preeclampsia characterized by hypertension proteinuria and kidney damage. We hypothesize that administration of VEGF121 may neutralize circulating sFlt-1, therefore reduce blood pressure, and the antihypertensive effects of VEGF121 may be more obvious in sFlt-1-mediated hypertension than that in normotensive. Female Sprague Dawley rats were intraperitoneally implanted with DSI radiotransmitters prior to intravenous injection of adenovirus expressing sFlt-1 genes at a dose of 6 × 1011 viral particle/kg (Adv-sFlt-1) and saline (control). VEGF121 was intravenously infused at 10 μg/kg/min for 180 minutes. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP), and heart rate were continuously monitored and analyzed during the VEGF121 infusion and up to 24 hours post VEGF121 infusion. SBP was increased by 17 mmHg from the baseline 5 days post Adv-sFlt-1 transfection (P < 0.05) while the SBP of control rats remained in the baseline. No effects on SBP, DBP, MAP, PP and HR during and after VEGF infusion observed in control rats. The antihypertensive effects of VEGF121 was observed as early as 10 minutes after VEGF121 infusion and lasted for 24 hours in Adv-sFlt-1 transfected rats. VEGF121 abolishes BP increase induced by transfection of Adv-SFlt-1 (P < 0.05 vs. control). Data demonstrate the antihypertensive effects of VEGF121 is more obvious in hypertensive rats than normotensive rats, suggesting VEGF121 is a potent antihypertensive agent in the setting of hypertension, and may be used to treat hypertension that occurs in preeclamptic patients.