Targeted delivery of adenovirus expressing eNOS to the endothelium in vivo lowers blood pressure in hypertensive rats

Background: Vascular dysfunction associated with oxidative stress is a key feature of human essential hypertension. The stroke prone spontaneously hypertensive rat (SHRSP) is a model of this condition. We have shown that local in vivo application of adenovirus encoding for either endothelial nitric oxide synthase (eNOS) or extracellular superoxide dismutase (SOD3) improves impaired nitric oxide (NO) bioavailability and endothelial function in the carotid artery of the SHRSP (1,2). The present study sought to determine the effects of systemic administration of these vectors on blood pressure in the SHRSP. Since adenovirus is sequestered and degraded by the liver we also evaluated specific targeting of vectors to the vascular endothelium, using a bispecific antibody 3.