RGD Reference Report - Isoflurane favorably modulates guanosine triphosphate cyclohydrolase-1 and endothelial nitric oxide synthase during myocardial ischemia and reperfusion injury in rats.

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Isoflurane favorably modulates guanosine triphosphate cyclohydrolase-1 and endothelial nitric oxide synthase during myocardial ischemia and reperfusion injury in rats.
Authors:	Baotic, Ines Weihrauch, Dorothee Procknow, Jesse Vasquez-Vivar, Jeanette Ge, Zhi-Dong Sudhakaran, Shaan Warltier, David C Kersten, Judy R
Citation:	Baotic I, etal., Anesthesiology. 2015 Sep;123(3):582-9. doi: 10.1097/ALN.0000000000000778.
RGD ID:	329970290
Pubmed:	PMID:26192027 (View Abstract at PubMed)
PMCID:	PMC4543441 (View Article at PubMed Central)
DOI:	DOI:10.1097/ALN.0000000000000778 (Journal Full-text)
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.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
GCH1	Human	myocardial infarction	treatment	ISO	Gch1 (Rattus norvegicus)		RGD
Gch1	Rat	myocardial infarction	treatment	IEP			RGD
Gch1	Mouse	myocardial infarction	treatment	ISO	Gch1 (Rattus norvegicus)		RGD
NOS2	Human	myocardial infarction	treatment	ISO	Nos2 (Rattus norvegicus)		RGD
Nos2	Rat	myocardial infarction	treatment	IEP			RGD
Nos2	Mouse	myocardial infarction	treatment	ISO	Nos2 (Rattus norvegicus)		RGD

Objects Annotated

Genes (Rattus norvegicus)

Gch1 (GTP cyclohydrolase 1)

Nos2 (nitric oxide synthase 2)

Genes (Mus musculus)

Gch1 (GTP cyclohydrolase 1)

Nos2 (nitric oxide synthase 2, inducible)

Genes (Homo sapiens)

GCH1 (GTP cyclohydrolase 1)

NOS2 (nitric oxide synthase 2)

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Isoflurane favorably modulates guanosine triphosphate cyclohydrolase-1 and endothelial nitric oxide synthase during myocardial ischemia and reperfusion injury in rats.