Adverse effects of tempol on hidrosaline balance in rats with acute sodium overload

We studied the effects of tempol, an oxygen radical scavenger, on hydrosaline balance in rats with acute sodium overload. Male rats with free access to water were injected with isotonic (control group) or hypertonic saline solution (0.80 mol/l NaCl) either alone (Na group) or with tempol (Na-T group). Hydrosaline balance was determined during a 90 min experimental period. Protein expressions of aquaporin 1 (AQP1), aquaporin 2 (AQP2), angiotensin II (Ang II) and endothelial nitric oxide synthase (eNOS) were measured in renal tissue. Water intake, creatinine clearance, diuresis and natriuresis increased in the Na group. Under conditions of sodium overload, tempol increased plasma sodium and protein levels and increased diuresis, natriuresis and sodium excretion. Tempol also decreased water intake without affecting creatinine clearance. AQP1 and eNOS were increased and Ang II decreased in the renal cortex of the Na group, whereas AQP2 was increased in the renal medulla. Nonglycosylated AQP1 and eNOS were increased further in the renal cortex of the Na-T group, whereas AQP2 was decreased in the renal medulla and was localized mainly in the cell membrane. Moreover, p47-phox immunostaining was increased in the hypothalamus of Na group, and this increase was prevented by tempol. Our findings suggest that tempol causes hypernatremia after acute sodium overload by inhibiting the thirst mechanism and facilitating diuresis, despite increasing renal eNOS expression and natriuresis.     

Gyrate atrophy of the choroid and retina with hyperornithinemia: biochemical and histologic studies and response to vitamin B6.

Four patients with hyperomithinemia and gyrate atrophy of the choroid and retina age described. In vivo response to vitamin B6 is documented in three of the four patients by significant reduction of fasting serum ornithine and increase of lysine after oral B6 supplementation. Oral glucose tolerance testing in one patient resulted in marked changes in serum ornithine and lysine concentrations, in addition to mild glucose intolerance. Histochemical staining of punch muscle biopsies showed intracellular inclusions in type 2 muscle fibers. Tubular aggregates, approximately 60 nm in diameter and adjacent to the sarcoplasmic membrane, were seen on electron microscopy. Obligate heterozygotes had a mean serum ornithine slightly higher than normal, but there was considerable overlap with the normal range. Oral ornithine tolerance tests distinguished carriers from controls in only one of five cases. Deficient activity of ornithine ketoacid aminotransferase (OKT) in cultured skin fibroblasts was documented in all four patients. Approximately half-normal levels were found in obligate heterozygotes. In vitro response to B6 was manifest by increased OKT activity at increased concentrations of pyridoxal phosphate in fibroblasts from the patients.