Na(+), K(+)-ATPase content in skeletal muscle of dogs with pituitary-dependent hyperadrenocorticism.

Several hormones regulate Na(+), K(+)-ATPase content in the muscle cell membrane, which is essential for maintaining muscle cell excitability. Chronic glucocorticoid excess is associated with muscle weakness and reduced endurance. We hypothesized that chronic glucocorticoid excess affects Na(+), K(+)-ATPase content in canine skeletal muscle, and contributes to reduced endurance and muscle weakness associated with pituitary-dependent hyperadrenocorticism (PDH) in dogs. Therefore, Na(+), K(+)-ATPase content in skeletal muscle was evaluated before and after hypophysectomy and hormone replacement (cortisone and l-thyroxin) in dogs with PDH (n=13), and in healthy controls (n=6). In addition, baseline and exercise-induced changes in plasma electrolyte concentrations and acid-base balance were evaluated before and after hypophysectomy in dogs with PDH. Na(+), K(+)-ATPase content of gluteal muscle in dogs with PDH was significantly lower than in control dogs (201+/-13pmol/g versus 260+/-8pmol/g wet weight; P<0.01). Similar differences were found in palatine muscle. After hypophysectomy and on hormone replacement, Na(+), K(+)-ATPase was increased (234+/-7pmol/g wet weight). Both plasma pH and base excess in dogs with PDH (7.44+/-0.01; 1.7+/-0.6mmol/l, respectively) were significantly higher (P<0.05) than after hypophysectomy and hormone replacement (7.41+/-0.01; -0.2+/-0.4mmol/l, respectively). Exercise induced respiratory alkalosis, but did not result in hyperkalemia in dogs with PDH. In conclusion, chronic glucocorticoid excess in dogs with PDH is associated with decreased Na(+), K(+)-ATPase content in skeletal muscle. This may contribute to reduce endurance in canine PDH, although dogs with PDH did not exhibit exercise-induced hyperkalemia. Na(+), K(+)-ATPase content normalized to values statistically not different from healthy controls after hypophysectomy and hormone replacement.

Endothelial injury: cause and effect of alloimmune inflammation.

This review discusses the concept that endothelial cells may facilitate inflammation, but are also targets of the inflammatory response. Endothelial cells express several molecules that promote leukocyte recruitment, and other molecules, such as MHC class I that enable endothelial injury. Circulating alloantibodies produced following transplantation may also target the endothelium for injury. It has been shown that the expression of select protective genes within endothelial cells, including anti-apoptotic genes, may provide resistance to immune-mediated injury. Thus, an understanding of the mechanisms by which endothelial cells are injured and by which endothelial cells are protected is important for our understanding of allograft rejection.