Dexamethasone on inducible nitric oxide synthase and nitrite/nitrate production in myocardial infarction.
The effect of dexamethasone (DEX) on the activation of the inducible form of nitric oxide synthase (iNOS) and its relation to the formation of oxidation products of nitric oxide (NO2-+ NO3-, NOx) in infarcted heart muscle of rabbits was investigated. Myocardial infarction was produced by ligation of the first anterior branch of the left circumflex coronary artery. NOx was determined by chemiluminescence and iNOS by conversion of L-[14C]-arginine to L-[14C]-citrulline. The rise in myocardial iNOS production, which followed onset of myocardial ischemia, was suppressed by DEX. In addition, following coronary artery ligation, coronary arterial venous differences of NOx increased markedly; this effect was also partially abolished by DEX. Cardiac origin of NOx was confirmed by the linear relationship between coronary A-V NOx difference and myocardial formation of iNOS. This relationship was preserved after administration of DEX. Therefore glucocorticoids interfere with the myocardial NO production and thus diminish the concentration of its oxidative products in plasma.
Kimura
A
A
Huntington Medical Research Institutes, Department of Experimental Cardiology, Pasadena, California 91101, USA.
Roseto
J
J
Suh
K Y
KY
Bing
R J
RJ
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004790:Enzyme Induction / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism*; D011817:Rabbits
D005938:Glucocorticoids; D009566:Nitrates; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D003907:Dexamethasone; D019001:Nitric Oxide Synthase