Abstract
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.
Similar content being viewed by others
Article PDF
References
Baker KM, Booz GW, Dostal DE : Cardiac actions of angiotensin II: role of an intracardiac renin-angiotensin system. Annu Rev Physiol 1992; 54: 227–241.
Lindpaintner K, Ganten D : The cardiac renin-angiotensin system. An appraisal of present experimental and clinical evidence. Circ Res 1991; 68: 905–921.
Baker KM, Aceto JF : Angiotensin II stimulation of protein synthesis and cell growth in chick heart cells. Am J Physiol 1990; 259: H610–H618.
Nicholls MG, Robertson JI : The renin-angiotensin-system in the year 2000. J Hum Hypertens 2000; 10: 649–666.
Goette A, Staack T, Rocken C : Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation. J Am Coll Cardiol 2000; 35: 1669–1677.
Pederson OD, Bagger H, Kober L, Torop-Pederson C : Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction. Circulation 1999; 100: 376–380.
Van Den Berg MP, Crijns HJ, Van Veldhuisen DJ, Griep N, Dekam PJ, Liek I : Effects of lisinopril in patients with heart failure and chronic atrial fibrillation. J Card Fail 1995; 1: 355–364.
Nakashima H, Kumagai K, Urata H, Gondo N, Ideishi M, Arakawa K : Angiotensin II antagonist prevents electrical remodeling in atrial fibrillation. Circulation 2000; 101: 2612–2617.
Vermes E, Tardif JC, Bourassa MG, et al: Enalapril decreases the incidence of atrial fibrillation in patients with left ventricular dysfunction. Circulation 2003; 107: 2926–2931.
Madrid AH, Bueno MG, Rebollo JM, et al: Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation. A prospective and randomized study. Circulation 2002; 106: 331–336.
Kannel WB, Wolf PA, Benjamin EJ, Levy D : Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol 1998; 82: 2N–9N.
Dahlof B, Hornestam B, Aurup P : Losartan decreases the risk of stroke in hepertensive patients with atrial fibrillation and left ventricular hypertrophy. Eur Heart J 2002; 23: 412.
Wachtell K, Lehto M, Hornestam B, et al: Losartan reduces the risk of new-onset atrial fibrillation in hypertensive patients with electrocardiogram left-ventricular hypertrophy: the LIFE study. Eur Heart J 2003; 24: 504.
Sadoshima JI, Izumo S : Signal transduction pathway of angiotensin II-induced c-fos gene expression in cardiac myocytes in vitro. Circ Res 1993; 73: 424–438.
Bahinski A, Narin AC, Greengard P, Gadsby DC : Chloride conductance regulated by cyclic AMP-dependent protein kinase in cardiac myocytes. Nature 1989; 340: 718–721.
Tanaka Y, Hisatome I, Miyamoto J, et al: Enhancing effects of salicylate on tonic and phasic block of Na+ channels by Class 1 antiarrhythmic agents in the ventricular myocytes and the guinea pig papillary muscle. Biochim Biophys Acta 1999; 1418: 320–334.
Isenberg G, Klockner U : Calcium tolerant ventricular myocytes prepared by preincubation in a “KB medium.” Pflügers Arch 1982; 395: 6–18.
Hamil OP, Marty A, Neher E, Sakman B, Sigworth FJ : Improved patch-clap techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch 1981; 391: 85–100.
Tsutsumi Y, Matsubara H, Masaki H, et al: Angiotensin II type 2 receptor overexpression activates the vascular kinin system and causes vasodilation. J Clin Invest 1999; 104: 925–935.
Jia N, Okamoto H, Shimizu T, et al: A newly developed angiotensin II type I receptor antagonist, CS866, promotes regression of cardiac hypertrophy by reducing integrin β1 expression. Hypertens Res 2003; 26: 737–742.
Bonnardeaux JL, Regoli D : Action of angiotensin and analogues on the heart. Can J Physiol Pharmacol 1974; 52: 50–60.
Chen SA, Chang MS, Chiang BN, Cheng KK, Lin CI : Electromechanical effects of angiotensin in human atrial tissues. J Mol Cell Cardiol 1991; 23: 483–493.
Habuchi Y, Lu LL, Morikawa J, Yoshimura M : Angiotensin II inhibition of L-type Ca2+ current in sinoaterial node cells of rabbits. Am J Physiol 1995; 268: H1053–H1060.
Morita H, Kimura J, Endoh M : Angiotensin II activation of a chloride current in rabbit cardiac myocytes. J Physiol (Lond) 1995; 483: 119–130.
Cox MH, Gasparo M, Mukherjee R, Hewett KW, Spinale FG : Myocardial electrophysiological properties in the presence of an AT1 angiotensin II receptor antagonist. Basic Res Cardiol 1997; 92: 129–138.
Obayashi K, Horie M, Xie LH, et al: Angiotensin II inhibits protein kinase A-dependent chloride conductance in heart via pertussis toxin-sensitive G proteins. Circulation 1997; 95: 197–204.
Miura S, Saku K, Karnik SS : Molecular analysis of the structure and function of the angiotensin II type 1 receptor. Hypertens Res 2003; 26: 937–943.
Mizuno M, Sada T, Ikeda M, et al: Pharmacology of CS-866, a novel nonpeptide angiotensin II receptor antagonist. Eur J Pharmacol 1995; 285: 181–188.
Chorvatova A, Gallo-Payet N, Casanova C, Payet MD : Modulation of membrane potential and ionic currents by the AT1 and AT2 receptors of angiotensin II. Cell Signal 1996; 8: 525–532.
Yu H, Gao J, Wang H, et al: Effects of the renin-angiotensin system on the current Ito in epicardial and endocardial ventricular myocytes from canine heart. Circ Res 2000; 86: 1062–1068.
Tsuchiya K, Horie M, Watanuki M, et al: Functional compartmentalization of ATP is involved in angiotensin II-mediated closure of cardiac ATP-sensitive K+ channels. Circulation 1997; 96: 3129–3135.
Komuro I, Kaida T, Shibazaki Y, et al: Stretching cardiac myocytes stimulates protooncogene expression. J Biol Chem 1990; 265: 3595–3598.
Kumagai K, Nakashima H, Urata H, et al: Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardiol 2003; 41: 2197–2204.
Zou Y, Akazawa H, Qin Y, et al: Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II. Nat Cell Biol 2004; 6: 499–506.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sonoyama, K., Igawa, O., Miake, Ji. et al. Effects of Angiotensin II on the Action Potential Durations of Atrial Myocytes in Hypertensive Rats. Hypertens Res 28, 173–179 (2005). https://doi.org/10.1291/hypres.28.173
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1291/hypres.28.173
Keywords
This article is cited by
-
Effects of magnesium supplementation on electrophysiological remodeling of cardiac myocytes in L-NAME induced hypertensive rats
Journal of Bioenergetics and Biomembranes (2016)