Cardiac-specific overexpression of angiotensin II AT2 receptor causes attenuated response to AT1 receptor-mediated pressor and chronotropic effects

The Journal of Clinical Investigation
H MasakiHiroaki Matsubara

Abstract

Angiotensin (Ang) II has two major receptor isoforms, AT1 and AT2. Currently, AT1 antagonists are undergoing clinical trials in patients with cardiovascular diseases. Treatment with AT1 antagonists causes elevation of plasma Ang II which selectively binds to AT2 and exerts as yet undefined effects. Cardiac AT2 level is low in adult hearts, whereas its distribution ratio is increased during cardiac remodeling and its action is enhanced by application of AT1 antagonists. Although in AT2 knock-out mice sensitivity to the pressor action of Ang II was increased, underlying mechanisms remain undefined. Here, we report the unexpected finding that cardiac-specific overexpression of the AT2 gene using alpha-myosin heavy chain promoter resulted in decreased sensitivity to AT1-mediated pressor and chronotropic actions. AT2 protein undetectable in the hearts of wild-type mice was overexpressed in atria and ventricles of the AT2 transgenic (TG) mice and the proportions of AT2 relative to AT1 were 41% in atria and 45% in ventricles. No obvious morphological change was observed in the myocardium and there was no significant difference in cardiac development or heart to body weight ratio between wild-type and TG mice. Infusion of Ang II to AT2...Continue Reading

References

Jan 1, 1992·Annual Review of Physiology·K M BakerD E Dostal
Sep 1, 1991·The Journal of Clinical Investigation·E F GradyJ E Kalinyak
Mar 1, 1972·Circulation Research·C M FerrarioJ W McCubbin
Dec 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·J W GordonF H Ruddle
Jul 16, 1982·European Journal of Pharmacology·A NakashimaC I Johnston
Nov 7, 1995·Proceedings of the National Academy of Sciences of the United States of America·M NakajimaV J Dzau
Jan 1, 1995·The Journal of Clinical Investigation·Y NioM Inada
Dec 15, 1993·Biochemical and Biophysical Research Communications·M NakajimaV J Dzau
Jan 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·T YamadaV J Dzau
Jun 21, 1996·The Journal of Biological Chemistry·J Zhang, R E Pratt
Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·Y A LeeK Lindpaintner
Aug 1, 1996·Journal of Molecular and Cellular Cardiology·M BrinkG Bullock
Jun 10, 1997·Proceedings of the National Academy of Sciences of the United States of America·L HeinV J Dzau
Aug 1, 1997·Journal of Molecular and Cellular Cardiology·C A van KesterenA H Danser

❮ Previous
Next ❯

Citations

Apr 6, 2001·Clinical Cardiology·P CarsonH M Siragy
Mar 25, 2011·Pediatric Cardiology·Kee Soo HaJoo Won Lee
Jul 8, 2003·Current Hypertension Reports·Rubin ZhangEfrain Reisin
Sep 12, 2000·Current Hypertension Reports·R M CareyH M Siragy
Apr 6, 2000·The American Journal of Cardiology·B H Lorell
Dec 4, 2003·The Journal of Laboratory and Clinical Medicine·Liming WangRobert F Spurney
Oct 9, 2001·Clinical Therapeutics·K Dickstein
Oct 16, 2001·Regulatory Peptides·J M SaavedraT Inagami
Jul 8, 1999·Regulatory Peptides·M de Gasparo, H M Siragy
Jan 5, 2000·Molecular and Cellular Endocrinology·E M WintourN Tenis
Nov 5, 1999·Trends in Endocrinology and Metabolism : TEM·M HoriuchiL Daviet
Feb 1, 2000·Trends in Endocrinology and Metabolism : TEM·S Nouet, C Nahmias
Dec 1, 2001·Trends in Cardiovascular Medicine·T Inagami, T Senbonmatsu
Mar 21, 2002·Clinical and Experimental Pharmacology & Physiology·T Morgan
Sep 24, 1999·Current Opinion in Nephrology and Hypertension·T H Le, T M Coffman
Dec 18, 2003·Clinical and Experimental Pharmacology & Physiology·Yi-Chun ZhuTai Yao
Jan 8, 2000·Fundamental & Clinical Pharmacology·M GervaisJ F Giudicelli
Dec 1, 2004·Basic & Clinical Pharmacology & Toxicology·Angelica WackenforsMalin Malmsjö
Jun 29, 2000·Annual Review of Biochemistry·D L Garbers, S K Dubois
Oct 8, 1999·The Journal of Clinical Investigation·Y TsutsumiT Iwasaka
Feb 28, 2002·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Hiroaki Matsubara
Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·P ParadisM Nemer
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·H M SiragyR M Carey
Sep 15, 1998·Lancet·J G ClelandP A Poole-Wilson
May 6, 2014·Current Hypertension Reports·Elena KaschinaU Muscha Steckelings
Feb 22, 2012·Expert Opinion on Investigational Drugs·Koen VerdonkJoep H M van Esch
Jul 16, 2003·The American Journal of the Medical Sciences·Ursula C BrewsterMark A Perazella

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.