title: AT1 receptor antisense therapy transiently lowers blood pressure in Ren-2 transgenic rats.
abstract: 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.
authors.affiliation: Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. ivvn@medicon.cz
authors.forename: Ivana
authors.initials: I
authors.lastname: Vanecková
authors.forename: Libor
authors.initials: L
authors.lastname: Kopkan
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Husková
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Vanourková
authors.forename: Stanislava
authors.initials: S
authors.lastname: Schejbalová
authors.forename: Ludek
authors.initials: L
authors.lastname: Cervenka
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Kramer
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D006973:Hypertension / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000517:prevention & control; D008297:Male; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000627:therapeutic use*; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D012083:Renin / Q000235:genetics; D013599:Systole / Q000187:drug effects; D013872:Thionucleosides / Q000627:therapeutic use
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D020319:Oligodeoxyribonucleotides, Antisense; D044140:Receptor, Angiotensin, Type 1; D013872:Thionucleosides; D012083:Renin