Aortic coarctation induces oxidative stress in rat tissues.

The purpose of this study was to evaluate the induction of oxidative stress in heart and erythrocytes from rats with abdominal aorta coarctation (Coa) compared with sham-operated normotensive controls (Sham). The group of Coa animals developed myocardial hypertrophy, showing heart homogenates markedly increased levels of reduced glutathione (48%), lipid peroxidation (148%) and activation of superoxide dismutase and glutathione peroxidase (189% and 37%, respectively), compared with controls. Other oxidative stress indicators were also altered in erythrocytes from Coa rats: increased protein carbonyl content (141%) and total glutathione level (349%) were determined. Inactivation of the antioxidant enzymes catalase (27%), superoxide dismutase (58%) and glutathione peroxidase (25%) was observed in erythrocytes from the Coa group. Taken jointly our results provide strong evidence for the production of oxidative stress in heart and erythrocytes from aortic coarcted rats.

Expression of NOX-I, gp91phox, p47phox and P67phox in the aorta segments above and below coarctation.

Aorta coarctation results in hypertension (HTN) in the arterial tree proximal to stenosis and, as such, provides an ideal model to discern the effects of different levels of blood pressure on the vascular tissue in the same animal. Compelling evidence has emerged supporting the role of oxidative stress as a cause of HTN. However, whether or not HTN (independent of the circulating humoral factors) can cause oxidative stress is less certain. NAD(P)H oxidase isoforms are the main source of reactive oxygen species (ROS) in the vascular tissues. We therefore compared the expressions of NOX-I, gp91phox and the regulatory subunits of the enzyme in the aorta segments residing above and below coarctation in rats with abdominal aorta banding. Rats were studied 4 weeks after aorta banding above the renal arteries or sham operation. Subunits of NAD(P)H oxidase and its NOX-I isoform as well as endothelial NO synthase (eNOS) and nitrotyrosine (footprint of NO oxidation by superoxide) were measured in the aorta segments above and below coarctation. The gp91phox, p47phox, and p67phox subunits of NAD(P)H oxidase, NOX-I isoform, eNOS and nitrotyrosine were markedly increased in the aorta segment above coarctation (hypertensive zone), but were virtually unchanged in the segment below coarctation. Since, excepting blood pressure, all other conditions were constant, the upregulation of NAD(P)H oxidase isoforms and the increased NO oxidation in the aorta segment above, but not below, coarctation prove that HTN, per se, independent of circulating mediators can cause oxidative/nitrosative stress in the arterial wall. These observations suggest that HTN control may represent a specific form of antioxidant therapy for hypertensive disorders.

Renal cytochrome P-450-related arachidonate metabolism in rabbit aortic coarctation.

Cells of the medullary segment of the thick ascending limb of Henle's loop (TALH) convert arachidonic acid (AA) via the cytochrome P-450 monooxygenase pathway to biologically active metabolites: P1, a vasorelaxant, and P2, an inhibitor of Na+-K+-ATPase activity. These AA metabolites may contribute to the renal vascular and metabolic adjustments in response to renal hypoperfusion and the attendant elevation of blood pressure produced by suprarenal aortic coarctation. On the eighth postoperative day, the blood pressures of hypertensive and sham-operated control rabbits were 105 (90-115) and 63 (60-64) mmHg (medians with semiquartile values), respectively (P less than 0.01). Formation of P1 and P2 was increased twofold in TALH cells obtained from hypertensive rabbits: 2.35 (1.79-4.83) and 1.28 (1.56-4.56) micrograms AA converted.mg protein-1.30 min-1 compared with sham-operated rabbits: 1.27 (1.03-1.53) and 0.64 (0.58-1.10) micrograms AA converted.mg protein-1.30 min-1 (P less than 0.05). The profile of biological activity of AA metabolites contained within P1 and P2 was unaffected by aortic coarctation. The cytochrome P-450 monooxygenase-derived AA metabolites may exert a defensive function to limit the degree of TALH cell injury in response to renal hypoperfusion and associated zonal anoxia by reducing energy-dependent Na+-K+-ATPase activity and affecting local vasodilatation.

Muscle substrate levels, muscle enzyme activities and muscle morphology in the vastus lateralis and deltoideus muscles in normal children and in children with coarctation of the aorta.

Muscle biopsies from the deltoideus dx and vastus lat. dx muscles were taken in 17 children with coarctation of the aorta, aged 5.0 to 13.8 years, prior to surgery. Higher concentrations of glycogen, ATP and CP were found in the vastus lat. muscle compared to the deltoideus muscle. The same differences between these two muscles were also found in healthy controls. No differences were found between the patients with coarctation of the aorta and the control group. Nor were any differences found for the other variables studied; glucose, glucose-6-phosphate, lactate, muscle enzyme activities (SDH, LDH and phosphorylase), muscle fibre composition or fibre sizes. It seems reasonable to assume that the differences in muscle substrate levels found between the vasus lat. and the deltoideus muscles in the two groups were due to a higher degree of activity during daily life for the legs as compared to the arms. Patients with coarctation of the aorta do not seem to be influenced by the altered haemodynamic situation with regard to the studied variables.