Intravenous angiotensinogen antisense in AAV-based vector decreases hypertension

• Published in: American journal of physiology. Heart and circulatory physiology 1999-12, Vol.277 (6), p.H2392-H2399
• Main Authors: Tang, Xiaoping, Mohuczy, Dagmara, Zhang, Y. Clare, Kimura, Birgitta, Galli, Sara M, Phillips, M. Ian
• Format: Article
• Language: English
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.1999.277.6.H2392

Department of Physiology, College of Medicine, University of Florida, Gainesville, Florida 32610 Angiotensinogen (AGT) has been linked to hypertension. Because there are no direct inhibitors of AGT, we have developed antisense (AS) inhibition of AGT mRNA delivered in an adeno-associated virus (AAV)-based plasmid vector. This plasmid, driven by the cytomegalovirus promoter, contains a green fluorescent protein reporter gene and AS cDNA for rat AGT. Transfection of the plasmid into rat hepatoma cells brought a strong expression of the transgenes and a significant reduction in the level of AGT. In the in vivo study, naked plasmid DNA was intravenously injected into adult spontaneously hypertensive rats at different doses (0.6, 1.5, and 3 mg/kg). Expression of AGT AS mRNA was present in liver and heart, and it lasted longer in the liver. All three doses produced a significant decrease in blood pressure (BP). BP decreased for 2, 4, and 6 days, respectively. The lowest dose decreased BP by 12 ± 3.0 mmHg, whereas the higher doses decreased BP by up to 22.5 ± 5.2 mmHg compared with the control rats injected with saline ( P