Direct action of an angiotensin II receptor blocker on angiotensin II-induced left atrial conduction delay in spontaneously hypertensive rats.
In this study, the inhibitory action of angiotensin II (Ang II) receptor blocker (ARB) on Ang II-induced conduction blocking in the left atrium was studied. Transmembrane action potentials and effective refractory period (ERP) were recorded from the left atrial trabeculae of spontaneously hypertensive rats (SHR(Izm)s) that had been treated with or without olmesartan medoxomil (AT1 receptor blocker, 3.0 mg kg(-1)) for 8 weeks before the recording. During rapid electrical stimulation (RES), changes in activation time (AT) and frequencies of the conduction block were studied under perfusion of Ang II (10(-8) M) or Ang II plus ARB (10(-7) M). Interstitial fibrosis in the left atrium was quantitatively assessed using histological sections. Although action potential parameters and ERP did not differ between the two groups when preparations were driven with a basic cycle length, an Ang II-induced conduction delay was observed during RES, and this was significantly suppressed in SHR(Izm)s treated with ARB (P<0.05). The Ang II-induced conduction block was also significantly reduced with perfusion of ARB (P<0.05). The interstitial fibrous area was significantly larger in untreated SHR(Izm)s than in treated animals (P<0.01). This antagonizing action of AT1 blockade might contribute to its non-antiarrhythmic therapeutic effect on atrial fibrillation because of its indirect and direct actions on the structural and functional remodeling of the left atrium.
Matsuyama
Narihisa
N
Department of Cardiology, Yamato Municipal Hospital, Yamato 242-8602, Kanagawa, Japan. yamamoto-clinic@jcom.home.ne.jp
Tsutsumi
Takeshi
T
Kubota
Nami
N
Nakajima
Toshiaki
T
Suzuki
Hiroshi
H
Takeyama
Youici
Y
D000200:Action Potentials / Q000187:drug effects; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004558:Electric Stimulation; D006325:Heart Atria / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013777:Tetrazoles / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; C437965:olmesartan