Direct positive chronotropic action by angiotensin II in the isolated mouse atrium.
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.
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
Toyoki
T
Mori
Ayako
A
Hashimoto
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009248:Nadolol / Q000494:pharmacology; D013268:Stimulation, Chemical; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009248:Nadolol; D002216:Captopril; D019808:Losartan; D007545:Isoproterenol