Effects of selective nitric oxide synthase inhibition in hyperdynamic endotoxemia in dogs

被引:8
作者
Wolfárd, A
Kaszaki, J
Szabó, C
Balogh, Z
Nagy, S
Boros, M
机构
[1] Albert Szent Gyorgyi Med Univ, Inst Expt Surg, H-6701 Szeged, Hungary
[2] Childrens Hosp, Med Care Ctr, Div Crit Care Med, Cincinnati, OH USA
关键词
N-omega-nitro-L-arginine methyl ester; S-methylisothiourea; myocardial contractility; heart; nitric oxide synthase activity;
D O I
10.1159/000008708
中图分类号
R61 [外科手术学];
学科分类号
摘要
Objectives: Our aims were to investigate the systemic hemodynamic effects of constitutive endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) inhibitors in hyperdynamic endotoxemia. Patients and Methods: Group 1 comprised sham-operated controls, while in group 2, 3 and 4, a hyperdynamic circulatory reaction was elicited by a 2-hour infusion of Escherichia coli endotoxin (ETX) in a dose of 5.3 mu g/kg. The animals in group 3 were treated with 12.5 mg/kg nonselective NOS inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME), and those in group 4 with 2 mg/kg of the specific iNOS inhibitor S-methyl-isothiourea (SMT). Mean arterial pressure (MAP), cardiac output (CO) and myocardial contractility (MC) were measured, and total peripheral resistance (TPR) was calculated. The eNOS and iNOS activities were determined in myocardial biopsy samples taken after 8 h of endotoxemia. Results: ETX induced significant decreases in TPR and MAP, a transient myocardial depression, and increased the myocardial eNOS and iNOS activities. L-NAME decreased the activities of both isoenzymes, increased MC but induced a fall in CO. SMT inhibited iNOS by 60%, without influencing the eNOS activity, increased MAP and contractility in the early phase of endotoxemia, and induced only a slight decrease in CO. Conclusions: Nonselective NOS inhibition restores the arterial pressure and exerts a positive inotropic effect, but decreases CO. SMT selectively decreases the iNOS activation without disturbing the vasoregulatory function of the eNOS-derived nitric oxide in hyperdynamic endotoxemia in the dog.
引用
收藏
页码:314 / 323
页数:10
相关论文
共 30 条
[1]   Rapid increase in inducible nitric oxide synthase gene expression in the heart during endotoxemia [J].
Bateson, AN ;
Jakiwczyk, OM ;
Schulz, R .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1996, 303 (1-2) :141-144
[2]   MODULATION OF NITROGEN-OXIDE SYNTHESIS INVIVO - NG-MONOMETHYL-L-ARGININE INHIBITS ENDOTOXIN-INDUCED NITRITE NITRATE BIOSYNTHESIS WHILE PROMOTING HEPATIC DAMAGE [J].
BILLIAR, TR ;
CURRAN, RD ;
HARBRECHT, BG ;
STUEHR, DJ ;
DEMETRIS, AJ ;
SIMMONS, RL .
JOURNAL OF LEUKOCYTE BIOLOGY, 1990, 48 (06) :565-569
[3]   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
[4]  
Carleton Steven C., 1995, Cardiology Clinics, V13, P249
[5]   Animal models of sepsis and shock: A review and lessons learned [J].
Deitch, EA .
SHOCK, 1998, 9 (01) :1-11
[6]  
GOLDFARB RD, 1982, CIRC SHOCK, V9, P633
[7]  
HENDERSON JL, 1994, ARCH SURG-CHICAGO, V129, P1271
[8]   Nitric oxide synthase inhibition partially prevents decreased LV contractility during endotoxemia [J].
Herbertson, MJ ;
Werner, HA ;
Walley, KR .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1996, 270 (06) :H1979-H1984
[9]   Effects of N-omega-nitro-L-arginine methyl ester on the endotoxin-induced disseminated intravascular coagulation in porcine septic shock [J].
Jourdain, M ;
Tourneys, A ;
Leroy, X ;
Mangalaboyi, J ;
Fourrier, F ;
Goudemand, J ;
Gosselin, B ;
Vallet, B ;
Chopin, C .
CRITICAL CARE MEDICINE, 1997, 25 (03) :452-459
[10]   Effect of nitric oxide synthase inhibition on myocardial contractility in anesthetized normal and endotoxemic dogs [J].
Kaszaki, J ;
Wolfard, A ;
Bari, F ;
Boros, M ;
Parratt, JR ;
Nagy, S .
SHOCK, 1996, 6 (04) :279-285