TABLE 3.
Selected effects of peroxynitrite with potential relevance to cardiovascular pathophysiology
| Effect(s) | Reference Nos. |
|---|---|
| Inhibition of BH4-dependent, NAD-dependent and antioxidant enzymes | Reviewed in 1227 |
| Depletion of antioxidants (e.g., glutathione, cysteine) | Reviewed in 1227 |
| Increased lipid peroxidation | Reviewed in 1227 |
| Impairment of mitochondrial respiration and energy metabolism (inactivation of cytochromes, NADH-COQ1, etc.) | 144, 740, 1380 |
| Promotion of Ca2+-dependent mitochondrial permeability transition pore opening | 142, 999, 1000 |
| Inhibition of myocardial aconitase | 211 |
| Impairment of α1-, β1-, and β2-adrenoceptors, vasopressin VIA and ANG II receptor function | 84, 704–706, 751, 752 |
| Inactivation of myofibrillar creatine kinase and impairment of contractile function | 614, 877, 882 |
| Inactivation of α-actinin in cardiomyocytes | 117 |
| Inactivation of sarcoplasmic reticulum Ca2+-ATPase in myocytes and vascular smooth muscle, Ca2+ dysregulation | 483, 789, 1329 |
| Activation of myocardial matrix metalloproteinases (S-glutoxidation of prometalloproteinases) | 1345, reviewed in 995 |
| Alterations in signaling (activation of extracellular signal-related kinase; activation or inhibition of NFκB; nitration of PKC-ε-promoting translocation and activation) | 52, 749, 1024, 1178 |
| Activation or inactivation of cardiovascular K+ ATP channel(s) | 83, 471, 473, 783 |
| Inactivation voltage-gated K+ K(v) and Ca2+-activated K+ channels in coronary arterioles | 754, 785, 786 |
| Impairment of vascular relaxation by various mechanisms | 83, 469, 471, 473, 705, 879 |
| Inactivation of vascular prostacyclin synthase | 228, 290, 1466, 1467, 1472, 1475 |
| Uncoupling of NO synthase leading to production of superoxide rather than NO | 405–407, 734, 889 |
| Cardiac ion channel modulation?, arrhythmia | 1179, 1268 |
| Upregulation of adhesion molecules in endothelial cells, endothelial glycocalyx disruption, enhanced neutrophils adhesion (presumably via NFκB activation) | 424, 723, 1178, 1447, 1477 |
| Pro- or antiaggregatory effects on platelets depending on the environment | 908, 953; reviewed in 1097 |
| Apoptosis in cardiomyocytes, vascular endothelial and smooth muscle cells as a consequence of mitochondrial injury, DNA injury, caspase activation, signal transduction disturbances, calcium dysregulation | 30, 319, 480, 750, 755, 756, 879 |
| DNA damage, PARP activation, cell necrosis in cardiomyocytes, vascular endothelial and smooth muscle cells as a consequence of mitochondrial injury, energetic collapse, oxidation, nitration, antioxidant depletion, calcium dysregulation | 444, 1233, 1243, 1244, 1450; reviewed in 995, 1230, 1235 |
ANG II, angiotensin II; BH4, tetrahydrobiopterin; NFκB, nuclear factor kappa B; PARP, poly(ADP-ribose) polymerase; NO, nitric oxide.