Circulation Research, Vol 73, 898-905, Copyright © 1993 by American Heart Association

ARTICLES

Hypertensive rats produced by in vivo introduction of the human renin gene

N Tomita, J Higaki, Y Kaneda, H Yu, R Morishita, H Mikami and T Ogihara
Department of Geriatric Medicine, Osaka University Medical School, Japan.

We established an efficient and nontoxic in vivo gene transfer method mediated by the Sendai virus (hemagglutinating virus of Japan [HVJ]), liposomes, and nuclear protein. In this study, to produce a hypertensive model rat that is dependent on human renin, the human renin gene was introduced into adult rat liver by our efficient in vivo gene transfer method using HVJ and liposomes (HVJ-liposomes). The rats treated with HVJ-liposomes containing the human renin gene showed a significant elevation of blood pressure for 6 days compared with control rats, which received injections of HVJ-liposomes without the human renin gene. On day 5 after the transfer, human active renin as well as angiotensin II were found in the plasma of rats in which the human renin gene was introduced. Moreover, the blood pressure of these rats was significantly correlated with the plasma levels of human active renin and angiotensin II. To confirm that the elevated blood pressure was due to the expression of the human renin gene, we administered a newly developed specific human renin inhibitor, FK 906. The elevated blood pressure was normalized by the intravenous administration of this drug. These data indicate that this hypertensive rat was produced by the in vivo transfer of the human renin gene into rat liver and that the expressed human renin cleaved rat substrate (angiotensinogen). This hypertensive rat produced by in vivo gene transfer should be useful in further studies on hypertension.

This article has been cited by other articles:

				N. TOMITA, R. MORISHITA, H. Y. LAN, K. YAMAMOTO, M. HASHIZUME, M. NOTAKE, K. TOYOSAWA, B. FUJITANI, W. MU, D. J. NIKOLIC-PATERSON, et al. In Vivo Administration of a Nuclear Transcription Factor-{kappa}B Decoy Suppresses Experimental Crescentic Glomerulonephritis J. Am. Soc. Nephrol., July 1, 2000; 11(7): 1244 - 1252. [Abstract] [Full Text]

				T. Tomita, H. Takano, N. Tomita, R. Morishita, M. Kaneko, K. Shi, K. Takahi, T. Nakase, Y. Kaneda, H. Yoshikawa, et al. Transcription factor decoy for NF{kappa}B inhibits cytokine and adhesion molecule expressions in synovial cells derived from rheumatoid arthritis Rheumatology, July 1, 2000; 39(7): 749 - 757. [Abstract] [Full Text] [PDF]

				M. K. Raizada, M. J. Katovich, H. Wang, K. H. Berecek, and C. H. Gelband Is antisense gene therapy a step in the right direction in the control of hypertension? Am J Physiol Heart Circ Physiol, August 1, 1999; 277(2): H423 - H432. [Full Text] [PDF]

				S. Nakamura, A. Moriguchi, R. Morishita, K. Yamada, T. Nishii, N. Tomita, M. Ohishi, Y. Kaneda, J. Higaki, and T. Ogihara Activation of the Brain Angiotensin System by In Vivo Human Angiotensin-Converting Enzyme Gene Transfer in Rats Hypertension, August 1, 1999; 34(2): 302 - 308. [Abstract] [Full Text] [PDF]

				S. Tomita, N. Tomita, T. Yamada, L. Zhang, Y. Kaneda, R. Morishita, T. Ogihara, V. J. Dzau, and M. Horiuchi Transcription Factor Decoy to Study the Molecular Mechanism of Negative Regulation of Renin Gene Expression in the Liver In Vivo Circ. Res., May 14, 1999; 84(9): 1059 - 1066. [Abstract] [Full Text] [PDF]

				Y. Sawa, K. Kadoba, K. Suzuki, H.-Z. Bai, Y. Kaneda, R. Shirakura, and H. Matsuda EFFICIENT GENE TRANSFER METHOD INTO THE WHOLE HEART THROUGH THE CORONARY ARTERY WITH HEMAGGLUTINATING VIRUS OF JAPAN LIPOSOME J. Thorac. Cardiovasc. Surg., March 1, 1997; 113(3): 512 - 519. [Abstract] [Full Text]

				R. Morishita, J. Higaki, N. Tomita, M. Aoki, A. Moriguchi, K. Tamura, K. Murakami, Y. Kaneda, and T. Ogihara Role of Transcriptional cis-Elements, Angiotensinogen Gene–Activating Elements, of Angiotensinogen Gene in Blood Pressure Regulation Hypertension, March 1, 1996; 27(3): 502 - 507. [Abstract] [Full Text]

				Y. Sawa, K. Suzuki, H.-Z. Bai, R. Shirakura, R. Morishita, Y. Kaneda, and H. Matsuda Efficiency of In Vivo Gene Transfection Into Transplanted Rat Heart by Coronary Infusion of HVJ Liposome Circulation, November 1, 1995; 92(9): 479 - 482. [Abstract] [Full Text]

				N. Tomita, R. Morishita, J. Higaki, M. Aoki, Y. Nakamura, H. Mikami, A. Fukamizu, K. Murakami, Y. Kaneda, and T. Ogihara Transient Decrease in High Blood Pressure by In Vivo Transfer of Antisense Oligodeoxynucleotides Against Rat Angiotensinogen Hypertension, July 1, 1995; 26(1): 131 - 136. [Abstract] [Full Text]