Direct positive chronotropic action by angiotensin II in the isolated mouse atrium |
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Authors: | Mori Toyoki Hashimoto Ayako |
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Institution: | Research Institute of Pharmacological and Therapeutical Development, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno Kawauchi-cho, Tokushima 771-0192, Japan. to_mori@research.otsuka.co.jp |
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Abstract: | We observed the direct positive chronotropic effect of angiotensin II in mouse atria and characterized its pharmacological property. C57BL/6J mice were anesthetized with pentobarbital and hearts were quickly excised. Atrial preparations including right and left atrium were isolated and suspended in the organ bath filled with Krebs-Henseleit solution gassed with 95% O2 and 5% CO2. Angiotensin II at concentrations of 10(-10) to 10(-6) M caused concentration-dependent increase in heart rate, and the maximal response was about 13% of that by isoproterenol. The effect was blocked by the selective AT1-receptor antagonist, losartan at concentrations of 10(-6) M, but not by the selective beta-blocker, nadolol at concentration of 10(-5) M. Furthermore, angiotensin I also caused concentration-dependent increase in heart rate, and the effect was blocked by angiotensin converting enzyme (ACE) inhibitor, captopril at concentrations of 10(-6) M. These results suggested that angiotensin I is converted to angiotensin II via ACE system in mice atria, and regulate heart rate through AT1-receptor stimulation, not by beta-adrenergic receptor. |
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Keywords: | Heart rate C57BL/6 mice Angiotensin I Angiotensin II |
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