Induction of angiotensin II subtype 2 receptor-mediated blood pressure regulation in synthetic diet-fed rats

Autor: Masaaki Tamura, Alan Steimle, Miles A. Tanner, Paul R. Myers, Eric F. Howard, Erwin J. Landon, Tetsuo Takagi
Rok vydání: 2000
Předmět:
Male
Captopril
Pyridines
Physiology
Indomethacin
Gene Expression
Hemodynamics
Angiotensin-Converting Enzyme Inhibitors
Blood Pressure
Weight Gain
Rats
Sprague-Dawley
Norepinephrine
Vasoconstrictor Agents
Enzyme Inhibitors
Aorta
Receptors
Angiotensin
biology
Angiotensin II
Imidazoles
Receptor antagonist
Vasodilation
NG-Nitroarginine Methyl Ester
Losartan
Cardiology and Cardiovascular Medicine
Signal Transduction
medicine.drug
medicine.medical_specialty
Mean arterial pressure
Epinephrine
medicine.drug_class
Receptor
Angiotensin
Type 2
Receptor
Angiotensin
Type 1
Cardiac Glycosides
Angiotensin Receptor Antagonists
Internal medicine
Renin–angiotensin system
Internal Medicine
medicine
Animals
RNA
Messenger
Dose-Response Relationship
Drug
business.industry
Angiotensin-converting enzyme
Diet
Rats
Disease Models
Animal
Blood pressure
Endocrinology
biology.protein
business
Zdroj: Journal of Hypertension. 18:1239-1246
ISSN: 0263-6352
DOI: 10.1097/00004872-200018090-00010
Popis: Objective Chronic feeding of a purified synthetic diet induces renin-angiotensin system-dependent moderate high blood pressure in normal Sprague-Dawley rats. The present study was designed to characterize the angiotensin II (Ang II) receptor type 2 (AT 2 )-specific mechanism of blood pressure regulation in these rats. Methods The effect of the AT 2 receptor antagonist PD123319 (PD) on blood pressure was examined in vivo in synthetic diet-fed rats. Ang II-dependent contraction of aortic rings prepared from the synthetic diet-fed rats was also investigated. Results After 8 weeks of feeding the synthetic diet, the mean arterial pressure (MAP) was significantly elevated above levels measured in control rats (117 ± 2 versus 102 ± 3 mmHg, P< 0.05). Intravenous administration of PD to conscious hypertensive rats elicited an immediate dose-dependent increase in MAP that was sustained for approximately 7.4 min with 3 mg/kg PD. The angiotensin converting enzyme inhibitor captopril, but not the Ang II type 1 receptor blocker losartan, significantly attenuated the effect of PD on blood pressure. PD did not increase the plasma level of catecholamines. The PD-dependent blood pressure increase was not observed in normotensive control rats. Aortic ring assays revealed that functional activation of the AT 2 receptor occurs only in the hypertensive rats, and this AT 2 response is abolished by indomethacin (5 μmol/l) but not by N ω -nitro-L-arginine methyl ester (100 μmol/l). Conclusion These results clearly demonstrate that AT 2 receptor-mediated blood pressure regulation is functional in this experimental model of hypertension. Furthermore, cyclooxygenase metabolites might be the key mediators for the AT 2 receptor-mediated blood pressure-lowering action.
Databáze: OpenAIRE
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