The role of AT2 angiotensin II receptors in blood presure control and in the pathogenesis of two-kidney, one-clip Goldblatt hypertension
Project goals
The renin-angiotensin system (RAS) plays a key role in the regulation of arterial blood pressure (BP) and development of hypertension. The main peptide of the RAS is angiotensin II (ANG II). Most "classical" biological effects of ANG II are attributed toactivation of AT1 receprtors. Recently, evidence has accumulated that activation of AT2 receptors physiologically antagonizes the effects of ANG II caused by AT1 receptor activation. The aim of our study is to determine whether or not AT2 receptors indeed play a physiological role in the BP control and the development of hypertension. For this purpose, the effects of AT2 receptors blockade on the course of Goldblatt hypertension are to be studied. Also studied will be the possible role of AT2 receptorsin mediating the interaction of the RAS with the kallikrein-kinin system and nitric oxide in the development of hypertension. For this purpose AT1A receptor and B2 receptor knockout mice, will be used.
Keywords
Goldblatt hypertensionAT2 angiotenzin II receptorsrenin/angiotensin systemblood pressure
Public support
Provider
Academy of Sciences of the Czech Republic
Programme
Grants of distinctly investigative character focused on the sphere of research pursued at present particularly in the Academy of Sciences of the Czech Republic
Call for proposals
Výzkumné granty 2 (SAV02002-AB)
Main participants
Institut klinické a experimentální medicíny
Contest type
VS - Public tender
Contract ID
—
Alternative language
Project name in Czech
Úloha AT2 receptorů pro angiotenzin II v regulaci krevního tlaku a patogenezi Goldblattovské hypertenzi
Annotation in Czech
Renin-angiotenzinový systém (RAS) má klíčovou úlohu v regulaci výše arteriálního krevního tlaku (TK) a rozvoji hypertenze. Hlavním peptidem RAS je angiotenzin II (ANG II), který působí přes dva hlavní receptory, AT1, a AT2. Většina "klasických" biologických účinků ANG II je připisována aktivaci AT1 receptorů. V poslední době přibývá důkazů, že aktivace AT2 receptorů fyziologicky antagonizuje účinky ANG II způsobené aktivací AT 1 receptory. Cílem naší studie je ověřit, zda AT2 receptory mají skutečně významnou fyziologickou úlohu v regulaci TK a kompenzaci nepřiměřeně zvýšená aktivity RAS. K tomuto účelu bude studován vliv akutní achronické blokády AT2 receptorů na výši TK a průběh Goldblatovské hypertenze. Dále bude studována možná úloha AT2 receptorův zprostředkování interakce RAS s systémem kallikrein-kininovým a oxidem dusnatým v regulaci TK a rozvoji hypertenze. K tomuto účelu budou použity kmeny AT1A receptor a B2 receptor deficientní myši.
Scientific branches
R&D category
ZV - Basic research
CEP classification - main branch
FA - Cardiovascular diseases including cardio-surgery
CEP - secondary branch
FE - Other fields of internal medicine
CEP - another secondary branch
FP - Other medical fields
30106 - Anatomy and morphology (plant science to be 1.6)
30107 - Medicinal chemistry
30108 - Toxicology
30109 - Pathology
30201 - Cardiac and Cardiovascular systems
30217 - Urology and nephrology
30218 - General and internal medicine
30219 - Gastroenterology and hepatology
30220 - Andrology
30221 - Critical care medicine and Emergency medicine
30223 - Anaesthesiology
30224 - Radiology, nuclear medicine and medical imaging
30225 - Allergy
30226 - Rheumatology
30227 - Geriatrics and gerontology
30229 - Integrative and complementary medicine (alternative practice systems)
30230 - Other clinical medicine subjects
30307 - Nursing
30308 - Nutrition, Dietetics
30309 - Tropical medicine
30310 - Parasitology
30311 - Medical ethics
30312 - Substance abuse
30501 - Forensic science
30502 - Other medical science
Completed project evaluation
Provider evaluation
U - Uspěl podle zadání (s publikovanými či patentovanými výsledky atd.)
Project results evaluation
Since the AT2 receptor blockade did not either modify the develop. of hypertension or the blood pressure responses to nitric oxide synthase in two-kidney, one-clip hypertens. mice, the activation of AT2 receptors does not play a major role in this model.
Solution timeline
Realization period - beginning
Jan 1, 2002
Realization period - end
Jan 1, 2004
Project status
U - Finished project
Latest support payment
—
Data delivery to CEP
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data delivery code
CEP/2005/AV0/AV05IA/U/N/5:3
Data delivery date
Sep 26, 2007
Finance
Total approved costs
859 thou. CZK
Public financial support
280 thou. CZK
Other public sources
192 thou. CZK
Non public and foreign sources
387 thou. CZK
Basic information
Recognised costs
859 CZK thou.
Public support
280 CZK thou.
32%
Provider
Academy of Sciences of the Czech Republic
CEP
FA - Cardiovascular diseases including cardio-surgery
Solution period
01. 01. 2002 - 01. 01. 2004