Pivotal role of angiotensin II receptor subtype 1A in the development of two-kidney, one-clip hypertension: study in angiotensin II receptor subtype 1A knockout mice

• Published in: Journal of hypertension Vol. 26; no. 7; pp. 1379 - 1389
• Main Authors: Červenka, Luděk, Vaněčková, Ivana, Husková, Zuzana, Vaňourková, Zdenka, Erbanová, Michaela, Thumová, Monika, Škaroupková, Petra, Opočenský, Martin, Malý, Jan, Chábová, Věra Čertíková, Tesař, Vladimír, Bürgelová, Marcela, Viklický, Ondřej, Teplan, Vladimír, Želízko, Michal, Kramer, Herbert J, Navar, L Gabriel
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins, Inc 01-07-2008; Lippincott Williams & Wilkins
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Disease Models, Animal; Hypertension - genetics; Hypertension - physiopathology; Ligation; Male; Medical sciences; Mice; Mice, Knockout; Nitric Oxide Synthase - physiology; Receptor, Angiotensin, Type 1 - genetics; Receptor, Angiotensin, Type 1 - physiology; Receptor, Angiotensin, Type 2 - genetics; Receptor, Angiotensin, Type 2 - physiology; Renal Artery; Renin-Angiotensin System - physiology; Hypertension; two-kidney; Enzyme; Peptide hormone; Rodentia; angiotensin II receptor subtype 1 B; Cardiovascular disease; Nitric-oxide synthase; angiotensin II receptor subtype 1A knockout mice; Clip; Octapeptide; Vertebrata; Renin angiotensin system; one-clip Goldblatt hypertension; Mammalia; angiotensin II type 2 receptor; Mouse; Animal; Oxidoreductases; nitric oxide synthase; Angiotensin II; plasma and kidney angiotensin II levels; renin-angiotensin system
• ISSN: 0263-6352; 1473-5598
• DOI: 10.1097/HJH.0b013e3282fe6eaa

OBJECTIVEThe present study was performed to examine in two-kidney, one-clip (2K1C) Goldblatt hypertensive micefirst, the relative contribution of angiotensin II receptor subtypes 1A (AT1A) and 1B (AT1B); second, the role of angiotensin II type 2 (AT2) receptors in the development of hypertension in wild-type (AT1A+/+) and AT1A receptor knockout (AT1A−/−) mice; and third, the role of increased nitric oxide synthase activity in counteracting the hypertensinogenic action of angiotensin II in this model.
METHODSAT1A+/+ and AT1A−/− mice underwent clipping of one renal artery and were infused with either saline vehicle or selective AT2 receptor agonist CGP-42112A (CGP). Blood pressure was monitored by radiotelemetry. Blood pressure responses to the nitric oxide synthase inhibitor nitro-L-arginine-methyl-ester were evaluated.
RESULTSAT1A+/+ mice responded to clipping by a rise in blood pressure that was not modified by CGP infusion. Clip placement caused a slight increase in blood pressure in AT1A−/− mice that remained significantly lower than in AT1A+/+ mice. Acute nitric oxide synthase inhibition caused greater increase in blood pressure in 2K1C/AT1A+/+ than in AT1A+/+ mice.
CONCLUSIONThe present data support the critical role of AT1A receptors in the development of 2K1C hypertension, whereas AT1B receptors play only a minor role in blood pressure regulation in this model of angiotensin II-dependent hypertension. Activation of AT2 receptors does not play an antagonistic role in the AT1 receptor-mediated hypertensinogenic actions of angiotensin II in this model. Finally, enhanced nitric oxide synthase activity plays a protective role by counteracting the vasoconstrictor influences of angiotensin II in 2K1C hypertensive mice.