Permanent inhibition of angiotensinogen synthesis by antisense RNA expression

Hypertension
M SchinkeMichael Bader

Abstract

The renin-angiotensin system plays a pivotal role in blood pressure regulation. Recent molecular biological findings led to the new concept that in addition to the classic endocrine system, local tissue systems may also play an important role in cardiovascular diseases such as hypertension. In particular, the brain renin-angiotensin system was shown to influence the central control of blood pressure and is thought to contribute to the hypertensive phenotype of genetically hypertensive rat models. To identify the physiological role of these local systems, we established an antisense strategy to downregulate the expression of the precursor hormone angiotensinogen (AOGEN) in cell culture, which can also be used to establish transgenic rat lines. Plasmids encoding an RNA sequence complementary to the rat AOGEN mRNA under control of different viral and tissue-specific promoters were constructed and transfected into an AOGEN-expressing cell line. A competitive reverse transcription-polymerase chain reaction method was established for the quantification of AOGEN mRNA. Depending on the level of antisense RNA, the expression of the AOGEN gene was reduced down to 22% of control levels. Furthermore, the secretion of AOGEN protein was tota...Continue Reading

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Citations

Oct 6, 1997·Neurochemistry International·B WeissM Morabito
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·M SchinkeM Bader
Mar 8, 2013·Autonomic Neuroscience : Basic & Clinical·Erin L O'CallaghanAndrew M Allen
Jan 7, 1999·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·M Bader
May 16, 2002·Clinical and Experimental Pharmacology & Physiology·Debra I DizDavid B Averill
Jan 24, 2002·Journal of the American Society of Nephrology : JASN·Nengjen Remi ShihNorimoto Yanagawa

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