Regulation of heart mitochondrial nitric oxide synthase (mtNOS) by oxygen

VALDEZ LB; ZAOBORNYJ T; BOMBICINO S; IGLESIAS DE; BOVERIS A

Mitochondrial Free Radical Patophysiology

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Lugar: Kerala; Año: 2010;

Different nitric oxide synthase (NOS) isoforms are localized in heart in specific cellular microdomains: endothelial NOS (eNOS) is localized in the caveolae, neuronal NOS (nNOS) is found in the cardiac sarcoplasmic reticulum, and mitochondrial NOS (mtNOS) is localized in the inner mitochondrial membrane. Mitochondria are the largest cell consumers of O2 and the key determinants of cytosolic PO2 and of the O2 gradient between alveoli and tissues. In physiological conditions, not only Ca2+ level but also O2 concentration (KM = 40 M) are the main factors involved in the regulation of mtNOS activity. In this way, the in vivo enzymatic activity of heart mtNOS is about 25% of the maximal activity (about 2 nmol/min.mg protein). In turn, NO exhibits two main effects on the mitochondrial respiratory chain: the competitive inhibition of cytochrome oxidase and the stimulation of superoxide anion (O2-) production by inhibition of electron transfer at complex III. Rats submitted to chronic hypoxia in a hypobaric chamber or at high altitude showed an increase in heart mtNOS activity and expression, while rats submitted to acute hemorrhage or rabbit heart submitted to ex vivo ischemia-reperfusion, both situations producing an acute hypoxia, decreased mtNOS activity, without modification of mtNOS expression.