(Circulation. 1995;92:2683-2689.)
© 1995 American Heart Association, Inc.
Articles |
Angiotensin II Augments Cytokine-Stimulated Nitric Oxide Synthesis in Rat Cardiac Myocytes
From the Department of Cardiology, Jichi Medical School, Tochigi, and the Department of Internal Medicine, First Division, Kobe University School of Medicine (Y.K., M.Y.), Japan.
Correspondence to Uichi Ikeda, MD, Department of Cardiology, Jichi Medical School, Minamikawachi, Tochigi 329-04, Japan.
Background Nitric oxide (NO) has been shown to modulate cardiac function. We investigated the effect of angiotensin II (Ang II) on NO synthase activity in cardiac myocytes.
Methods and Results Using the Griess reagent, we measured the production of nitrite, a stable metabolite of NO, by cultured neonatal rat cardiac myocytes. The expression of inducible NO synthase (iNOS) mRNA was assayed by Northern blotting. Incubation of cardiac myocytes for 24 hours with interleukin-1ß (IL-1ß) caused a significant increase in NO production. Ang II significantly augmented NO synthesis in IL-1ß–stimulated but not in unstimulated cells in a dose-dependent manner. The angiotensin type I receptor antagonist CV 11974 inhibited the effect of Ang II dose-dependently. Simultaneous incubation of Ang II with NG-monomethyl-L-arginine or actinomycin D also completely inhibited the effect of Ang II. The Ang II–induced NO production by IL-1ß–stimulated cells was accompanied by increased iNOS mRNA accumulation. Phorbol 12-myristate 13-acetate (PMA) also augmented NO synthesis in IL-1ß–stimulated but not in unstimulated cells in a dose-dependent manner. The protein kinase C inhibitor calphostin C dose-dependently blocked the effect of Ang II. After protein kinase C activity was functionally depleted by treatment of cells with PMA for 24 hours, Ang II did not augment IL-1ß–induced NO production.
Conclusions These results indicate that Ang II upregulates IL-1ß–induced iNOS expression in cardiac myocytes, which is mediated at least partially via activation of protein kinase C.
Key Words: interleukins • angiotensin • receptors • endothelium-derived factors • muscle, smooth
This article has been cited by other articles:
 |
|
 |
|
  P. Castro-Chaves, R. Fontes-Carvalho, M. Pintalhao, P. Pimentel-Nunes, and A. F. Leite-Moreira Angiotensin II-induced increase in myocardial distensibility and its modulation by the endocardial endothelium in the rabbit heart Exp Physiol, June 1, 2009; 94(6): 665 - 674. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-X. Zhang, X.-M. Lu, S. Kimura, and A. Nishiyama Role of mitochondria in angiotensin II-induced reactive oxygen species and mitogen-activated protein kinase activation Cardiovasc Res, November 1, 2007; 76(2): 204 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Jia, M. Takahashi, H. Morimoto, S. Takahashi, A. Izawa, H. Ise, T. Iwasaki, H. Hattori, K.-J. Wu, and U. Ikeda Changes in cardiac lipid metabolism during sepsis: The essential role of very low-density lipoprotein receptors Cardiovasc Res, February 1, 2006; 69(2): 545 - 555. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Grishko, V. Pastukh, V. Solodushko, M. Gillespie, J. Azuma, and S. Schaffer Apoptotic cascade initiated by angiotensin II in neonatal cardiomyocytes: role of DNA damage Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2364 - H2372. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. W. Cowley Jr., T. Mori, D. Mattson, and A.-P. Zou Role of renal NO production in the regulation of medullary blood flow Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2003; 284(6): R1355 - R1369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Ikeda, Y. Maeda, K. Yamamoto, and K. Shimada C-Reactive protein augments inducible nitric oxide synthase expression in cytokine-stimulated cardiac myocytes Cardiovasc Res, October 1, 2002; 56(1): 86 - 92. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L.P. Caforio, J. H. Goldman, M. K. Baig, N. J. Mahon, A. J. Haven, B. E. Souberbielle, D. W. Holt, A. G. Dalgleish, and W. J. McKenna Elevated serum levels of soluble interleukin-2 receptor, neopterin and {beta}-2-microglobulin in idiopathic dilated cardiomyopathy: relation to disease severity and autoimmune pathogenesis Eur J Heart Fail, March 1, 2001; 3(2): 155 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Abe, M. Tokumura, T. Ito, T. Murai, A. Takashima, and N. Ibii Involvement of iNOS in postischemic heart dysfunction of stroke-prone spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H668 - H673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Schwobel, T. Fischer, B. Lanz, and M. Mohaupt Angiotensin II receptor subtypes determine induced NO production in rat glomerular mesangial cells Am J Physiol Renal Physiol, December 1, 2000; 279(6): F1092 - F1100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kobayashi, T. Higashi, K. Hara, H. Shirataki, and H. Matsuoka Effects of imidapril on NOS expression and myocardial remodelling in failing heart of Dahl salt-sensitive hypertensive rats Cardiovasc Res, December 1, 1999; 44(3): 518 - 526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yasuda and W. Y. W. Lew Angiotensin II exacerbates lipopolysaccharide-induced contractile depression in rabbit cardiac myocytes Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1442 - H1449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tamura, S. Umemura, N. Nyui, K. Hibi, T. Ishigami, M. Kihara, Y. Toya, and M. Ishii Activation of angiotensinogen gene in cardiac myocytes by angiotensin II and mechanical stretch Am J Physiol Regulatory Integrative Comp Physiol, July 1, 1998; 275(1): R1 - R9. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yamamoto, Q. N. Dang, R. A. Kelly, and R. T. Lee Mechanical Strain Suppresses Inducible Nitric-oxide Synthase in Cardiac Myocytes J. Biol. Chem., May 8, 1998; 273(19): 11862 - 11866. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-L. Liu, H. Murakami, and I. H. Zucker Angiotensin II–Nitric Oxide Interaction on Sympathetic Outflow in Conscious Rabbits Circ. Res., March 9, 1998; 82(4): 496 - 502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Ikeda, Y. Maeda, H. Funayama, Y. Hojo, M. Ikeda, S. Minota, S. Kano, and K. Shimada Monocyte-vascular smooth muscle cell interaction enhances nitric oxide production Cardiovasc Res, March 1, 1998; 37(3): 820 - 825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-P. Zou, F. Wu, and A. W. Cowley Jr Protective Effect of Angiotensin II-Induced Increase in Nitric Oxide in the Renal Medullary Circulation Hypertension, January 1, 1998; 31(1): 271 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yamamoto, U. Ikeda, K. Okada, T. Saito, Y. Kawahara, M. Okuda, M. Yokoyama, and K. Shimada Arginine Vasopressin Increases Nitric Oxide Synthesis in Cytokine-Stimulated Rat Cardiac Myocytes Hypertension, November 1, 1997; 30(5): 1112 - 1120. [Abstract] [Full Text]
|
|
|
|
 |
|
 J.-L. Balligand and P. J. Cannon Nitric Oxide Synthases and Cardiac Muscle : Autocrine and Paracrine Influences Arterioscler Thromb Vasc Biol, October 1, 1997; 17(10): 1846 - 1858. [Abstract] [Full Text]
|
|
|
|
|
|
U. Ikeda, K. Kurosaki, K.-i. Ohya, and K. Shimada Adenosine stimulates nitric oxide synthesis in vascular smooth muscle cells Cardiovasc Res, July 1, 1997; 35(1): 168 - 174. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Kelly and T. W. Smith Cytokines and Cardiac Contractile Function Circulation, February 18, 1997; 95(4): 778 - 781. [Full Text]
|
|
|
|
|
|
U. Ikeda, K. Yamamoto, Y. Maeda, M. Shimpo, T. Kanbe, and K. Shimada Endothelin-1 Inhibits Nitric Oxide Synthesis in Vascular Smooth Muscle Cells Hypertension, January 1, 1997; 29(1): 65 - 69. [Abstract] [Full Text]
|
|
|
|
|
|
U. Ikeda, T. Kanbe, Y. Kawahara, M. Yokoyama, and K. Shimada Adrenomedullin Augments Inducible Nitric Oxide Synthase Expression in Cytokine-Stimulated Cardiac Myocytes Circulation, November 15, 1996; 94(10): 2560 - 2565. [Abstract] [Full Text]
|
|
|
|
|
|
R. A. Kelly, J.-L. Balligand, and T. W. Smith Nitric Oxide and Cardiac Function Circ. Res., September 1, 1996; 79(3): 363 - 380. [Full Text]
|
|
|
|
|
|
H. G. Llambi, F. Manni, P. L. Padula, O.A. Carretero, and C.M. Taquini Myocardial Contractility Is Modulated by Angiotensin II via Nitric Oxide Hypertension, March 1, 1996; 27(3): 704 - 708. [Abstract] [Full Text]
|
|
|
|
|
|
K. Tamura, Y. E. Chen, M. Lopez-Ilasaca, L. Daviet, N. Tamura, T. Ishigami, M. Akishita, I. Takasaki, Y. Tokita, R. E. Pratt, et al. Molecular Mechanism of Fibronectin Gene Activation by Cyclic Stretch in Vascular Smooth Muscle Cells J. Biol. Chem., October 27, 2000; 275(44): 34619 - 34627. [Abstract] [Full Text] [PDF]
|
|