Cardiac Angiotensin II Type 2 Receptor Activates the Kinin/NO System and Inhibits Fibrosis
| Autor: | Osamu Iba, Satoshi Kurisu, Kazuaki Chayama, Yasuhiro Teranishi, Takafumi Ishida, Hideo Matsuura, Katsuya Amano, Ryoji Ozono, Hiroaki Matsubara, Tetsuya Oshima, Hiroshi Sugino, Masayuki Kambe |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty Vascular smooth muscle Receptor Bradykinin B2 Heart Ventricles Bradykinin Mice Transgenic Biology Nitric Oxide Receptor Angiotensin Type 2 Receptor Angiotensin Type 1 Transforming Growth Factor beta1 Mice chemistry.chemical_compound Atrial natriuretic peptide Transforming Growth Factor beta Fibrosis Internal medicine Internal Medicine medicine Animals RNA Messenger Receptor Receptors Angiotensin Angiotensin II receptor type 1 Angiotensin II Receptors Bradykinin Kinin medicine.disease Coronary Vessels Mice Inbred C57BL Endocrinology chemistry Hypertrophy Left Ventricular Kallikreins Nitric Oxide Synthase Extracellular Space |
| Zdroj: | Hypertension. 41:99-107 |
| ISSN: | 1524-4563 0194-911X |
| Popis: | We have previously demonstrated that stimulation of the angiotensin (Ang) II type 2 receptor in vascular smooth muscle cells caused bradykinin production by activating kininogenase in transgenic mice. The aim of this study was to determine whether overexpression of AT 2 receptors in cardiomyocytes attenuates Ang II–induced cardiomyocyte hypertrophy or interstitial fibrosis through a kinin/nitric oxide (NO)-dependent mechanism in mice. Ang II (1.4 mg/kg per day) or vehicle was subcutaneously infused into transgenic mice and wild-type mice for 14 days. The amount of cardiac AT 2 receptor relative to AT 1 receptor in transgenic mice was 22% to 37%. Ang II caused similar elevations in systolic blood pressure (by ≈45 mm Hg) in transgenic mice and wild-type mice. Myocyte hypertrophy assessed by an increase in myocyte cross-sectional area, left ventricular mass, and atrial natriuretic peptide mRNA levels were similar in transgenic and wild-type mice. Ang II induced prominent perivascular fibrosis of the intramuscular coronary arteries, the extent of which was significantly less in transgenic mice than in wild-type mice. Inhibition of perivascular fibrosis in transgenic mice was abolished by cotreatment with HOE140, a bradykinin B 2 receptor antagonist, or L-NAME, an inhibitor of NO synthase. Cardiac kininogenase activity was markedly increased (≈2.6-fold, P 2 receptors and endothelial NO synthase were expressed in the vascular endothelium, whereas only B 2 receptors were present in fibroblasts. These results suggest that stimulation of AT 2 receptors present in cardiomyocytes attenuates perivascular fibrosis by a kinin/NO-dependent mechanism. However, the effect on the development of cardiomyocyte hypertrophy was not detected in this experimental setting. |
| Databáze: | OpenAIRE |
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