Aortic enzymes and lactate in high altitude-raised and cholesterol-fed rabbits.

Fourteen male rabbits born at elevation 4000 ft (first experimental series) were transferred at age of 2 months to elevation 12470 ft and raised there for 18 weeks. Half of the animals remained on a commercial rabbit chow (group H) while the other half was on the same diet supplemented with cholesterol (group C). Eight male rabbits raised at sea level served as controls (group S). Intima-media homogenates from the thoracic aortas were assayed for lactate dehydrogenase (LDH), malate dehydrogenase (MDH), lipoamide dehydrogenase, pyruvate kinase (PK), phosphofructokinase (PFK) and the lysosomal hydrolases beta-glucuronidase and N-acetyl-beta-glucosaminidase (NAGA). Aortic lactate and glucose were also measured. Thirty-two male rabbits (second experimental series) were subdivided into 4 groups. Rabbits were fed a cholesterol-supplemented diet not only at high altitude (8 rabbits matching group C) but also 8 animals raised at sea level. The degree of atherosclerosis in the aortas of these 4 groups was assessed by measuring the aortic cholesterol contents. Plasma cholesterol was also determined. In the aortas of the rabbits of group H the activity of PK was significantly elevated, and the activity of the lysosomal hydrolases significantly decreased compared with aortas of group S rabbits. There was no difference in the other enzyme activities or in the aortic glucose and lactate content of these groups. Cholesterol feeding of the animals of group C resulted in a significantly increased activity of the lysosomal hydrolases as well as of LDH and PK. The lipid analyses (second experimental series) revealed a trend to a lower concentration of aortic cholesterol in the high altitude than in the sea level animals, both fed a cholesterol diet, in spite of the higher plasma cholesterol concentrations in the high altitude animals. The low aortic lysosomal hydrolase activities in the high altitude rabbits are in accord with their comparatively lower susceptibility to experimental atherosclerosis. This metabolic feature may be due to a lower degree of exposure of these aortas to injurious factors, such as infections or lower blood pressure. The elevated activity of PK without increased lactate content in group H animals seems to parallel the well-known general adaptation of the organism to high altitude hypoxia, and does not indicate a metabolic switch toward anaerobic glycolysis.