Beneficial effect of heme oxygenase-1 expression on myocardial ischemia-reperfusion involves an increase in adiponectin in mildly diabetic rats

Transient reduction in coronary perfusion pressure in the isolated mouse heart increases microvascular resistance (paradoxical vasoconstriction) by an endothelium-mediated mechanism. To assess the presence and extent of paradoxical vasoconstriction in hearts from normal and diabetic rats and to determine whether increased heme oxygenase (HO)-1 expression and HO activity, using cobalt protoporphyrin (CoPP), attenuates coronary microvascular response, male Wistar rats were rendered diabetic with nicotinamide/streptozotocin for 2 wk and either CoPP or vehicle was administered by intraperitoneal injection weekly for 3 wk (0.5 mg/100 g body wt). The isolated beating nonworking heart was submitted to transient low perfusion pressure (20 mmHg), and coronary resistance (CR) was measured. During low perfusion pressure, CR increased and was associated with increased lactate release. In diabetic rats, CR was higher, HO-1 expression and endothelial nitric oxide synthase were downregulated, and inducible nitric oxide synthase and O2− were upregulated. After 3 wk of CoPP treatment, HO activity was significantly increased in the heart. Upregulation of HO-1 expression and HO activity by CoPP resulted in the abolition of paradoxical vasoconstriction and a reduction in oxidative ischemic damage. In addition, there was a marked increase in serum adiponectin. Elevated HO-1 expression was associated with increased expression of cardiac endothelial nitric oxide synthase, B-cell leukemia/lymphoma extra long, and phospho activator protein kinase levels and decreased levels of inducible nitric oxide synthase and malondialdehyde. These results suggest a critical role for HO-1 in microvascular tone control and myocardial protection during ischemia in both normal and mildly diabetic rats through the modulation of constitutive and inducible nitric oxide synthase expression and activity, and an increase in serum adiponectin.

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Nitrotyrosine, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) are increased in thyroid tumors from children and adolescents

Journal of Endocrinological Investigation ◽

10.1007/bf03345100 ◽

2002 ◽

Vol 25 (8) ◽

pp. 675-683 ◽

Cited By ~ 14

Author(s):

A. Patel ◽

C. Fenton ◽

R. Terrell ◽

P. A. Powers ◽

C. Dinauer ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Children And Adolescents ◽

Inducible Nitric Oxide Synthase ◽

Endothelial Nitric Oxide Synthase ◽

Thyroid Tumors ◽

Oxide Synthase ◽

Endothelial Nitric Oxide ◽

Inducible Nitric Oxide

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Endothelial Nitric Oxide Synthase Mediates the First and Inducible Nitric Oxide Synthase Mediates the Second Window of Desflurane-Induced Preconditioning

Journal of Cardiothoracic and Vascular Anesthesia ◽

10.1053/j.jvca.2012.04.015 ◽

2013 ◽

Vol 27 (3) ◽

pp. 494-501 ◽

Cited By ~ 8

Author(s):

Andreas Redel ◽

Jan Stumpner ◽

Thorsten M. Smul ◽

Markus Lange ◽

Virginija Jazbutyte ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Endothelial Nitric Oxide Synthase ◽

Oxide Synthase ◽

Endothelial Nitric Oxide ◽

Inducible Nitric Oxide

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Halothane and Isoflurane Inhibit Vasodilation Due to Constitutive but Not Inducible Nitric Oxide Synthase

Anesthesiology ◽

10.1097/00000542-199605000-00018 ◽

1996 ◽

Vol 84 (5) ◽

pp. 1156-1165 ◽

Cited By ~ 25

Author(s):

Zhiyi Zuo ◽

Alexandra Tichotsky ◽

Roger A. Johns

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Guanylyl Cyclase ◽

Endothelial Nitric Oxide Synthase ◽

Receptor Activation ◽

Isometric Tension ◽

Oxide Synthase ◽

Endothelial Nitric Oxide ◽

Inducible Nitric Oxide

Background Inhalational anesthetics inhibit the nitric oxide-guanylyl cyclase signaling pathway, but the site of this inhibition is not yet clear. This study was designed to test the hypothesis that receptor activation or downstream signaling events leading to nitric oxide synthase activation are important sites for this inhibition by comparing the effect of anesthetics on vasodilation caused by the calcium-dependent constitutive endothelial nitric oxide synthase versus the calcium-independent inducible nitric oxide synthase. Methods Endothelium-intact or -denuded rat thoracic aorta rings preincubated with or without lipopolysaccharide were mounted for isometric tension measurement, constricted with phenylephrine, then relaxed with methacholine in the presence or absence of halothane (1-3%) or isoflurane (1-3%). The cyclic guanosine 3,5-monophosphate content in the endothelium-denuded rings preincubated with or without lipopolysaccharide in the presence or absence of 3% halothane or 3% isoflurane was quantified by radioimmunoassay. The activity of partially purified inducible nitric oxide synthase from activated mouse macrophage was assayed in the presence or absence of halothane (1-4%) or isoflurane (1-5%) by the conversion of 3H-L-arginine to 3H-L-citrulline. Results Halothane and isoflurane inhibited methacholine-stimulated, nitric oxide-mediated vasorelaxation in endothelium-intact aortic rings. Neither halothane nor isoflurane affected the vasorelaxation caused by basal endothelial nitric oxide synthase or inducible nitric oxide synthase activity. Neither anesthetic altered the cyclic guanosine 3,5-monophosphate increase caused by inducible nitric oxide synthase in the lipopolysaccharide-treated rings. Conclusions The results demonstrated that halothane and isoflurane inhibit only receptor/calcium-activated nitric oxide synthase action and that direct inhibition of nitric oxide synthase, soluble guanylyl cyclase, or an interaction with nitric oxide are not responsible for anesthetic inhibition of endothelium-dependent vasorelaxation.

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