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Isoflurane favorably modulates guanosine triphosphate cyclohydrolase-1 and endothelial nitric oxide synthase during myocardial ischemia and reperfusion injury in rats. Anesthesiology 2015 Sep;123(3):582-9

Date

07/21/2015

Pubmed ID

26192027

Pubmed Central ID

PMC4543441

DOI

10.1097/ALN.0000000000000778

Abstract

BACKGROUND: The authors investigated the hypothesis that isoflurane modulates nitric oxide (NO) synthesis and protection against myocardial infarction through time-dependent changes in expression of key NO regulatory proteins, guanosine triphosphate cyclohydrolase (GTPCH)-1, the rate-limiting enzyme involved in the biosynthesis of tetrahydrobiopterin and endothelial nitric oxide synthase (eNOS).

METHODS: Myocardial infarct size, NO production (ozone-mediated chemiluminescence), GTPCH-1, and eNOS expression (real-time reverse transcriptase polymerase chain reaction and western blotting) were measured in male Wistar rats with or without anesthetic preconditioning (APC; 1.0 minimum alveolar concentration isoflurane for 30 min) and in the presence or absence of an inhibitor of GTPCH-1, 2,4-diamino-6-hydroxypyrimidine.

RESULTS: NO2 production (158 ± 16 and 150 ± 13 pmol/mg protein at baseline in control and APC groups, respectively) was significantly (P < 0.05) increased 1.5 ± 0.1 and 1.4 ± 0.1 fold by APC (n = 4) at 60 and 90 min of reperfusion, respectively, concomitantly, with increased expression of GTPCH-1 (1.3 ± 0.3 fold; n = 5) and eNOS (1.3 ± 0.2 fold; n = 5). In contrast, total NO (NO2 and NO3) was decreased after reperfusion in control experiments. Myocardial infarct size was decreased (43 ± 2% of the area at risk for infarction; n = 6) by APC compared with control experiments (57 ± 1%; n = 6). 2, 4-Diamino-6-hydroxypyrimidine decreased total NO production at baseline (221 ± 25 and 175 ± 31 pmol/mg protein at baseline in control and APC groups, respectively), abolished isoflurane-induced increases in NO at reperfusion, and prevented reductions of myocardial infarct size by APC (60 ± 2%; n = 6).

CONCLUSION: APC favorably modulated a NO biosynthetic pathway by up-regulating GTPCH-1 and eNOS, and this action contributed to protection of myocardium against ischemia and reperfusion injury.

Author List

Baotic I, Weihrauch D, Procknow J, Vasquez-Vivar J, Ge ZD, Sudhakaran S, Warltier DC, Kersten JR

Authors

Jeannette M. Vasquez-Vivar PhD Professor in the Biophysics department at Medical College of Wisconsin
Dorothee Weihrauch DVM, PhD Professor in the Anesthesiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Anesthetics, Inhalation
Animals
GTP Cyclohydrolase
Isoflurane
Male
Myocardial Ischemia
Myocardial Reperfusion Injury
Nitric Oxide Synthase Type III
Random Allocation
Rats
Rats, Wistar
jenkins-FCD Prod-399 190a069c593fb5498b7fcd942f44b7bc9cdc7ea1