Differential response to myocardial reperfusion injury in eNOS-deficient mice.
Two strains of endothelial nitric oxide synthase (eNOS)-deficient (-/-) mice have been developed that respond differently to myocardial ischemia-reperfusion (MI/R). We evaluated both strains of eNOS(-/-) mice in an in vivo model of MI/R. Harvard (Har) eNOS(-/-) mice (n = 12) experienced an 84% increase in myocardial necrosis compared with wild-type controls (P < 0.05). University of North Carolina (UNC) eNOS(-/-) (n = 10) exhibited a 52% reduction in myocardial injury versus wild-type controls (P < 0.05). PCR analysis of myocardial inducible NO synthase (iNOS) mRNA levels revealed a significant (P < 0.05) increase in the UNC eNOS(-/-) mice compared with wild-type mice, and there was no significant difference between the Har eNOS(-/-) and wild-type mice. UNC eNOS(-/-) mice treated with an iNOS inhibitor (1400W) exacerbated the extent of myocardial necrosis. When treated with 1400W, Har eNOS(-/-) did not exhibit a significant increase in myocardial necrosis. These data demonstrate that two distinct strains of eNOS(-/-) mice display opposite responses to MI/R. Although the protection seen in the UNC eNOS(-/-) mouse may result from compensatory increases in iNOS, other genes may be involved.
Sharp
Brent R
BR
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
Jones
Steven P
SP
Rimmer
David M
DM
Lefer
David J
DJ
D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western; D006339:Heart Rate; D006439:Hemodynamics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000503:physiopathology; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D009336:Necrosis; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011506:Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D011506:Proteins; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse