The effectiveness of antisense (AS) phosphorothioated oligodeoxynucleotides (AS-ODN) targeted to the angiotensin (ANG) type 1 (AT1) receptor, was studies in Ren-2 transgenic rats (TGR), whose ANG II-dependent hypertension can be attributed to the insertion of a single mouse renin gene. Our results show that a single intraarterial bolus injection of AT1-AS in 30-day-old rats results in a prolonged lowering of systolic blood pressure (SBP) for a period of 18 days with an average difference in SBP of 30 mm Hg between AS-treated and untreated TGR. No effect of AS therapy on SBP has been observed in control HanSD animals. However, at the end of the experiment, i.e. on day 100 of age, there were no differences in mean arterial pressure, proteinuria or cardiac hypertrophy between AS-treated and untreated TGR. Thus, no persistent effect of this therapy was observed after a single bolus injection. Collectively, the data show a prolonged antihypertensive effect of AT1 receptor antisense oligonucleotides during the developmental phase of hypertension in TGR when applied as a single treatment in prehypertensive animals which, however, does not persist up to the maintenance phase of hypertension in adulthood.
- MeSH
- Oligodeoxyribonucleotides, Antisense administration & dosage therapeutic use MeSH
- Angiotensin II Type 1 Receptor Blockers therapeutic use MeSH
- Financing, Organized MeSH
- Animals, Genetically Modified MeSH
- Hypertension drug therapy MeSH
- Hypertrophy, Left Ventricular prevention & control MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Rats, Sprague-Dawley MeSH
- Proteinuria drug therapy MeSH
- Receptor, Angiotensin, Type 1 genetics MeSH
- Renin genetics MeSH
- Systole drug effects MeSH
- Thionucleosides therapeutic use MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
