ANGIOTENSIN-II AUGMENTS CYTOKINE-STIMULATED NITRIC-OXIDE SYNTHESIS IN RAT CARDIAC MYOCYTES

被引:71
作者
IKEDA, U [1 ]
MAEDA, Y [1 ]
KAWAHARA, Y [1 ]
YOKOYAMA, M [1 ]
SHIMADA, K [1 ]
机构
[1] KOBE UNIV,SCH MED,DEPT INTERNAL MED,DIV 1,KOBE,JAPAN
关键词
INTERLEUKINS; ANGIOTENSIN; RECEPTOR; ENDOTHELIUM-DERIVED FACTORS; MUSCLE; SMOOTH;
D O I
10.1161/01.CIR.92.9.2683
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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-1 beta (IL-1 beta) caused a significant increase in NO production. Ang II significantly augmented NO synthesis in IL-1 beta-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 N-G-monomethyl-L-arginine or actinomycin D also completely inhibited the effect of Ang II. The Ang II-induced NO production by IL-1 beta-stimulated cells was accompanied by increased iNOS mRNA accumulation. Phorbol 12-myristate 13-acetate (PMA) also augmented NO syn thesis in IL-1 beta-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-1 beta-induced NO production. Conclusions These results indicate that Ang II upregulates IL-1 beta induced iNOS expression in cardiac myocytes, which is mediated at least partially via activation of protein kinase C.
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收藏
页码:2683 / 2689
页数:7
相关论文
共 51 条
[1]   CARDIAC ACTIONS OF ANGIOTENSIN-II - ROLE OF AN INTRACARDIAC RENIN-ANGIOTENSIN SYSTEM [J].
BAKER, KM ;
BOOZ, GW ;
DOSTAL, DE .
ANNUAL REVIEW OF PHYSIOLOGY, 1992, 54 :227-241
[2]   CONTROL OF CARDIAC-MUSCLE CELL-FUNCTION BY AN ENDOGENOUS NITRIC-OXIDE SIGNALING SYSTEM [J].
BALLIGAND, JL ;
KELLY, RA ;
MARSDEN, PA ;
SMITH, TW ;
MICHEL, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (01) :347-351
[3]   LEVELS OF T-LYMPHOCYTE SUBPOPULATIONS, INTERLEUKIN-1-BETA, AND SOLUBLE INTERLEUKIN-2 RECEPTOR IN ACUTE MYOCARDIAL-INFARCTION [J].
BLUM, A ;
SCLAROVSKY, S ;
REHAVIA, E ;
SHOHAT, B .
AMERICAN HEART JOURNAL, 1994, 127 (05) :1226-1230
[4]   NITRIC-OXIDE PRODUCTION WITHIN CARDIAC MYOCYTES REDUCES THEIR CONTRACTILITY IN ENDOTOXEMIA [J].
BRADY, AJB ;
POOLEWILSON, PA ;
HARDING, SE ;
WARREN, JB .
AMERICAN JOURNAL OF PHYSIOLOGY, 1992, 263 (06) :H1963-H1966
[5]  
Brady AJB, 1993, AM J PHYSIOL, P176
[6]   NOMENCLATURE FOR ANGIOTENSIN RECEPTORS - A REPORT OF THE NOMENCLATURE-COMMITTEE OF THE COUNCIL-FOR-HIGH-BLOOD-PRESSURE-RESEARCH [J].
BUMPUS, FM ;
CATT, KJ ;
CHIU, AT ;
DEGASPARO, M ;
GOODFRIEND, T ;
HUSAIN, A ;
PEACH, MJ ;
TAYLOR, DG ;
TIMMERMANS, PBMWM .
HYPERTENSION, 1991, 17 (05) :720-721
[7]   ANGIOTENSIN RECEPTOR SUBTYPES IN RAT, RABBIT AND MONKEY TISSUES - RELATIVE DISTRIBUTION AND SPECIES DEPENDENCY [J].
CHANG, RSL ;
LOTTI, VJ .
LIFE SCIENCES, 1991, 49 (20) :1485-1490
[8]   CYTOKINE GENE-TRANSCRIPTION IN VASCULARIZED ORGAN GRAFTS - ANALYSIS USING SEMIQUANTITATIVE POLYMERASE CHAIN-REACTION [J].
DALLMAN, MJ ;
LARSEN, CP ;
MORRIS, PJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 174 (02) :493-496
[9]   NITRIC-OXIDE SYNTHASE ACTIVITIES IN HUMAN MYOCARDIUM [J].
DEBELDER, AJ ;
RADOMSKI, MW ;
WHY, HJF ;
RICHARDSON, PJ ;
BUCKNALL, CA ;
SALAS, E ;
MARTIN, JF ;
MONCADA, S .
LANCET, 1993, 341 (8837) :84-85
[10]  
DUDLEY DT, 1990, MOL PHARMACOL, V38, P370