Role of mitochondrial function in cardiovascular adaptation to hemorrhage in conscious and anesthetized rats.

- FELLET A, VALDEZ L, ZAOBORNYJ T, CANIL A, VALLI G, ARRANZ C, BOVERIS A, BALASZCZUK AM.

Montevideo, Uruguay

Congreso; Free Radicals in Montevideo, V Meeting of SFRBM - South American Group and V International Conference on Peroxynitrite and Reactive Nitrogen Species; 2007

 Abstract: We recently reported that hypovolemic state induced by acute hemorrhage triggered a heterogeneous and dynamic nitric oxide synthases (NOS) activation modulating the cardiovascular response in anesthetized rats. The involvement of nitric oxide (NO) pathway occurs in an isoform-specific and time dependent manner. We demonstrated, for the first time, that increased cardiac endothelial NOS expression is an early molecular response to regulate heart rate after blood loss. The inducible NOS become a major source of cardiac NO production in the later stages, which could be determinant of the heart dysfunction after 120 min of sustained hemorrhagic shock. Our aim was to evaluate the involvement of mitochondrial NOS (mtNOS) activity in the cardiovascular adaptation to hemorrhagic shockc after 120 min of bleeding in conscious and anesthetized rats. The study comprised 3 groups of animals (n=5 per group): C: normotensive conscious and anesthetized rats; CH: conscious hemorrhaged rats (20% blood loss); AH: anesthetized hemorrhage rats. Heart mitochondria isolated from control, conscious and anesthetized hemorrhaged rats showed high respiratory control, indicating that the organelles were well coupled and able to effectively carry out oxidative phosphorylation (C=1.8; CH=1.8 and AH=1.5). No differences in the succinate-supported state 4 and 3 respiration (ng-at O/min.mg protein) were observed among the experimental groups (Cst4 = 130±9.8, Cst3 = 234±16; CHst4 = 112±10, CHst3 = 204±15; AHst4 = 158±11, AHst3 = 240±11). Blood loss did not modify heart mitochondrial hydrogen peroxide production (nmol H2O2/min.mg protein) compared with C (C=0.577±0.05; CH=0.569±0.1; AH=0.524±0.06). However, the hypovolemic state modified heart mtNOS functional activity determined by enhancing H2O2 production (C=59%; CH=85%; AH=67%). Taking into account that changes in mtNOS functional activity reflect variations in mitochondrial NO production and steady state concentration, higher mitochondrial NO levels would be involved in the cardiovascular adaptation to volume depletion observed in conscious animals.