Effects of PDGF A-chain antisense oligodeoxynucleotides on growth of cardiovascular organs in stroke-prone spontaneously hypertensive rats

We examined the effects of the platelet-derived growth factor (PDGF) A-chai n antisense oligodeoxynucleotides (ODN) on cardiovascular organ growth in s troke-prone spontaneously hypertensive rats (SHR-SP) in vivo. Expression of PDGF A-chain mRNA was higher in the aorta and kidney in 9-week-old SHR-SP than in Wistar-Kyoto (WKY) rats. A phosphorothioate-linked 15-mer antisense ODN complementary to the initiation codon region of rat PDGF A-chain mRNA and a control sense ODN were infused subcutaneously into SHR-SP/Izumo at a dose of 90 ng/g body weight/day for 28 days using an implanted ALZET pump. The PDGF A-chain antisense ODN did not affect blood pressure or body weight . The antisense ODN significantly inhibited [H-3]thymidine incorporation in to the DNA in the aorta and kidney but not in the heart. Infusion of the an tisense ODN considerably reduced production of PDGF A-chain protein but did not affect expression of PDGF A-chain mRNA. Infusion of the antisense ODN considerably improved the arterial and renal tissue damage in SHR-SP morpho logically. From these findings, it can be confirmed that suppression of PDG F A-chain by the antisense DNA is useful as a gene therapy for treating car diovascular organ damage in hypertension. (C) 2001 American Journal of Hype rtension, Ltd.