Monaco 2018 Am J Physiol Regul Integr Comp Physiol
|Monaco CMF, Miotto PM, Huber JS, van Loon LJC, Simpson JA, Holloway GP (2018) Sodium nitrate supplementation alters mitochondrial H2O2 emission but does not improve mitochondrial oxidative metabolism in the heart of healthy rats. Am J Physiol Regul Integr Comp Physiol 315:R191-R204.|
Abstract: Supplementation with dietary inorganic nitrate (NO3-) is increasingly recognized to confer cardioprotective effects in both healthy and clinical populations. While the mechanism(s) remains ambiguous, in skeletal muscle oral consumption of NaNO3 has been shown to improve mitochondrial efficiency. Whether NaNO3 has similar effects on mitochondria within the heart is unknown. Therefore, we comprehensively investigated the effect of NaNO3 supplementation on in vivo left ventricular (LV) function and mitochondrial bioenergetics. Healthy male Sprague-Dawley rats were supplemented with NaNO3 (1 g/l) in their drinking water for 7 days. Echocardiography and invasive hemodynamics were used to assess LV morphology and function. Blood pressure (BP) was measured by tail-cuff and invasive hemodynamics. Mitochondrial bioenergetics were measured in LV isolated mitochondria and permeabilized muscle fibers by high-resolution respirometry and fluorometry. Nitrate decreased (P < 0.05) BP, LV end-diastolic pressure, and maximal LV pressure. Rates of LV relaxation (when normalized to mean arterial pressure) tended (P = 0.13) to be higher with nitrate supplementation. However, nitrate did not alter LV mitochondrial respiration, coupling efficiency, or oxygen affinity in isolated mitochondria or permeabilized muscle fibers. In contrast, nitrate increased (P < 0.05) the propensity for mitochondrial H2O2 emission in the absence of changes in cellular redox state and decreased the sensitivity of mitochondria to ADP (apparent Km). These results add to the therapeutic potential of nitrate supplementation in cardiovascular diseases and suggest that nitrate may confer these beneficial effects via mitochondrial redox signaling.
Labels: MiParea: Respiration, Pharmacology;toxicology
Organism: Rat Tissue;cell: Heart Preparation: Permeabilized tissue, Isolated mitochondria
Regulation: ADP Coupling state: LEAK, OXPHOS Pathway: N, NS HRR: Oxygraph-2k