Effects of angiotensin II on the action potential durations of atrial myocytes in hypertensive rats.
Angiotensin II (Ang II) has been reported to indirectly influence atrial electrical activity and to play a critical role in atrial arrhythmias in hypertensive patients. However, it is unclear whether Ang II has direct effects on the electrophysiological activity of the atrium affected by hypertension. We examined the effects of Ang II on the action potentials of atrial myocytes enzymatically isolated from spontaneous hypertensive rats (SHRs). The action potentials were recorded by the perforated patch-clamp technique and the atrial expression of the receptors AT1a and AT2 was measured by radioimmunoassay. Ang II significantly shortened the action potential durations (APDs) of SHRs without changes in the resting membrane potentials (RMPs). Pretreatment with selective AT1a blockers abolished the Ang II-induced reduction of atrial APDs of SHRs; however, a selective AT2 blocker did not, which was consistent with the results of the receptor assay. Pretreatment with phosphatidylinositol 3 (PI3)-kinase inhibitor, phospholipase C inhibitor, or protein kinase C (PKC) inhibitor abolished the Ang II-induced shortening of atrial APDs, but pertussis toxin and protein kinase A (PKA) inhibitor did not. To study the effects of chronic AT1a inhibition on Ang II-induced shortening of atrial APD, SHRs were treated with AT1a blocker for 4 weeks. AT1a blocker abolished the Ang II-induced reduction of atrial APDs of SHRs and also significantly lowered their blood pressure. In conclusion, Ang II shortened atrial APDs of SHRs via AT1a coupled with the Gq-mediated inositol triphosphate (IP3)-PKC pathway. Our findings indicated that Ang II caused atrial arrhythmias in hypertensive patients by shortening the effective refractory period of the atrium.
Sonoyama
Kazuhiko
K
Department of Cardiovascular Medicine, Tottori University Faculty of Medicine, Yonago, Japan.
Igawa
Osamu
O
Miake
Jun-Ichiro
J
Yamamoto
Yasutaka
Y
Sugihara
Shinobu
S
Sasaki
Norihito
N
Shimoyama
Masaki
M
Hamada
Toshihiro
T
Taniguchi
Shin-Ichi
S
Yoshida
Akio
A
Ogino
Kazuhide
K
Shigemasa
Chiaki
C
Hoshikawa
Yoshiko
Y
Kurata
Yasutaka
Y
Shiota
Goshi
G
Narahashi
Toshio
T
Horiuchi
Masatsugu
M
Matsubara
Hiroaki
H
Ninomiya
Haruaki
H
Hisatome
Ichiro
I
D000200:Action Potentials / Q000187:drug effects*; D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011863:Radioimmunoassay; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects*; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects
D004791:Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II