Nitroprusside Increases Gene Transfer Associated with Intracoronary Delivery of Adenovirus

Abstract

Efficient gene transfer by vectors that can be easily delivered to target organs is desirable in clinical gene therapy. We tested the hypothesis that intracoronary infusion of the nitric oxide donor nitroprusside would increase the efficiency of adenovirus vector-mediated gene transfer to the heart. Intracoronary delivery of an adenovirus encoding murine adenylyl cyclase type VI (Ad.AC(VI)) was performed in adult pigs with and without simultaneous intracoronary infusion of nitroprusside. Animals were killed 12-14 days after Ad.AC(VI) delivery and myocardial adenylyl cyclase activity was measured. Addition of nitroprusside during intracoronary infusion of Ad.AC(VI) was associated with a 4-fold increase in cAMP-generating capacity in the left ventricle. Transgene expression was confirmed by immunoblotting. Intracoronary nitroprusside produced mild dose-dependent changes in blood pressure and heart rate during infusion. Intracoronary nitroprusside infusion is a safe and effective means to increase the extent of cardiac gene transfer with intracoronary delivery of adenovirus vectors.