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  • Title: Nitric oxide. An important signaling mechanism between vascular endothelium and parenchymal cells in the regulation of oxygen consumption.
    Author: Shen W, Hintze TH, Wolin MS.
    Journal: Circulation; 1995 Dec 15; 92(12):3505-12. PubMed ID: 8521573.
    Abstract:
    BACKGROUND: Nitric oxide (NO) is known to be an inhibitor of mitochondrial function. However, the physiological significance of endothelium-derived NO in the control of tissue respiration is not established. METHODS AND RESULTS: Tissue O2 consumption by skeletal muscle slices of the triceps brachii of normal dogs was measured with a Clark-type O2 electrode/tissue bath system at 37 degrees C. S-Nitroso-N-acetylpenicillamine (SNAP), carbachol (CCh), or bradykinin (BK) decreased tissue O2 consumption by 12 +/- 3% to 55 +/- 8%, 15 +/- 6% to 36 +/- 11%, or 21 +/- 5% to 42 +/- 4% at doses of 10(-7) to 10(-4) mol/L, respectively. The effects of both CCh and BK but not SNAP were eliminated by nitro-L-arginine (NLA, 10(-4) mol/L), consistent with SNAP decomposing to release NO and both CCh and BK stimulating endogenous NO production from L-arginine. Oxygen consumption was also decreased by 8-bromo-cGMP. The mitochondrial uncoupler dinitrophenol blocked the effects of 8-bromo-cGMP but only slightly altered those of SNAP, indicating that the major site of action of NO is the mitochondria. In normal, chronically instrumented, resting conscious dogs, blockade of NO synthase by NLA increased mean arterial pressure by 28 +/- 2.5 mm Hg and hind limb vascular resistance by 114 +/- 12% and decreased blood flow by 39 +/- 3%. Most important, NLA also increased O2 uptake by 55 +/- 9% in hind limb skeletal muscle (P < .05), associated with decreases in PO2 and O2 saturation and an increase in reduced hemoglobin in hind limb venous blood. CONCLUSIONS: Our results indicate that NO release from vascular endothelial cells appears to play an important physiological role in the regulation of tissue mitochondrial respiration in skeletal muscle and perhaps other organ systems.
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