Hypertensive RatsProduced byInVivo Introduction oftheHumanReninGene

We established an efficient andnontoxic invivogene transfer methodmediated bytheSendai virus (hemagglutinating virus ofJapan[HVJ]), liposomes, andnuclear protein. Inthisstudy, toproduce a hypertensive modelratthatisdependent on humanrenin, thehumanrenin gene was introduced into adult ratliver byourefficient invivo genetransfer methodusingHVJandliposomes (HVJ-liposomes). Theratstreated withHVJ-liposomes containing thehumanrenin geneshowed a significant elevation of blood pressurefor6dayscompared withcontrol rats, whichreceived injections ofHVJ-liposomes without thehumanrenin gene.Onday5after thetransfer, humanactive renin aswell asangiotensin IIwerefound intheplasma ofratsinwhichthehumanrenin genewas introduced. Moreover, theblood pressureofthese ratswas significantly correlated withtheplasmalevels ofhumanactive reninandangiotensin II. To confirm thattheelevated bloodpressurewas duetotheexpression ofthehumanreningene,we administered a newlydeveloped specific humanrenin inhibitor, FK906.Theelevated blood pressurewas normalized bytheintravenous administration ofthis drug. Thesedataindicate thatthis hypertensive rat was produced bytheinvivotransfer ofthehumanrenin geneinto ratliver andthattheexpressed human renincleaved ratsubstrate (angiotensinogen). Thishypertensive ratproduced byinvivo genetransfer should beuseful infurther studies on hypertension. (Circ Res.1993;73:898-905.)