Endothelium of the Myocardial Capillaries

Accumulating evidence suggests that oxygen stress alters many functions of the endothehum, including modulation of vasomotor tone (Cai and Harrison 2000). Inactivation of nitric oxide by superoxide and other reactive oxygen species seems to occur in conditions such as hypertension, hypercholesterol-aemia, diabetes and cigarette smoking. Loss of NO associated with these traditional risk factors may in part explain why they dispose to atherosclerosis. 

One of the earliest important events after reperfusion of an ischaemic vascular bed is a significant degree of endothelial dysfunction characterized by the loss of endothelium-derived relaxing factor 

Isolated pig coronary arteries with intact endothelium generated Oj at a rate of 9.0 0.8 pM per min and mg dry weight (Brandes et al. 1997) this rate was diminished by about 24% when the endothelium was removed. The nitroblue tetrazo-lium staining of arterial ring preparations showed formazan precipitation mainly in the intima. 

Human coronary artery endothelial cells were incubated with epinephrine (10 to 10 M) alone or with the water-soluble analogue of vitamin E (tro-lox) (10 M), the Upid-soluble vitamin E (5 X10 M), or the Pi-adrenergic blocker atenolol (10 M). At 1 and 24 h of incubation with epinephrine, superoxide anion generation increased by 102 and 81 % (Mehta and Li 2001). There was a marked increase in both MnSOD and Cu/ZnSOD mRNA and protein. Both MnSOD and Cu/ZnSOD activities were also increased. Pre-treatment of the cells with trolox and vitamin E decreased superoxide anion generation (P 0.05 vs. epinephrine alone) and blocked the subsequent upregulation of SOD mRNA and protein. Treatment of cells with the P-blocker atenolol also blocked the upregulation of SOD (P 0.05 vs. epinephrine alone). 

DNA damage was assessed in human umbihcal vein endothelial cells exposed to superoxide, hydrogen peroxide, nitric oxide, and peroxynitrite (Ballinger etal. 2000). In both vascular endotheUal and human aortic smooth muscle cells, the mitochondrial DNA was preferentially damaged relative to the transcriptionally inactive nuclear P-globulin gene. Similarly, a dose-dependent decrease in mtDNA-encoded mRNA transcripts was associated with reactive species treatment. Mitochondrial protein synthesis was also inhibited in a dose-dependent manner by peroxynitrite, resulting in decreased cellular ATP levels and mitochondrial redox function. 

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