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Abstract-We investigated the effects of uninephrectomy (UNX) in 6-week-old male and female rats on blood pressure (BP), renal sodium handling, salt sensitivity, oxidative stress, and renal injury over 18 months postsurgery, studying control sham-operated and UNX-operated rats at 6, 12, and 18 months postsurgery, evaluating their renal sodium handling, BP, urinary isoprostanes, N-acetyl-β-d-glucosaminidase, and proteinuria before and after a 2-week high-salt intake period. At 18 months, plasma variables were measured and kidney samples were taken for the analysis of renal morphology and tissue variables. BP was increased at 6 months in male UNX rats versus controls and at 12 and 18 months in both male and female UNX rats and was increased in male versus female UNX groups at 18 months. UNX did not affect water and sodium excretion under basal conditions and after the different test in male and female rats at different ages. However, the renal function curve was shifted to the right in both male and female UNX rats. Highsalt intake increased BP in both UNX groups at 6, 12, and 18 months and in the female control group at 18 months, and it increased proteinuria, N-acetyl-β-d-glucosaminidase, and isoprostanes in both UNX groups throughout the study. Renal lesions at 18 months were more severe in male versus female UNX rats. In summary, long-term UNX increased the BP, creatinine, proteinuria, pathological signs of renal injury, and salt sensitivity. Earlier BP elevation was observed and morphological lesions were more severe in male than in female UNX rats. Rodríguez-Gómez et al Effects of Uninephrectomy in Rats 1459scarcely more feasible to recruit living donors for the longterm follow-up of key renal functional and morphological parameters. With this background, the objective of the present study was to examine the consequences of UNX in male and female rats, as a model of donor nephrectomy, on BP, renal sodium handling, salt sensitivity, oxidative stress, and renal injury over 18 months and on renal pathology variables gathered at 18 months. Methods AnimalsMale and female Wistar rats born and raised in the experimental animal service of the University of Granada were used. Experiments were performed according to European Union guidelines for the ethical care of animals. At 6 weeks of age, the rats were divided into 4 groups (n=25 in each), 1 male and 1 female group for UNX and 1 male and 1 female group for sham operation (controls). In the UNX group, total extirpation of the left kidney was performed, leaving the adrenal gland intact. Sham-operated animals were prepared in the same manner, and the left kidney was handled but not removed. Postsurgery, all animals had access to standard chow and tap water ad libitum. Experimental ProtocolThe same experimental protocol was repeated in the same 8 rats from each study group at 6, 12, and 18 months after surgery in the following consecutive procedures: (1) for baseline, animals were housed in metabolic cages (Panlab, Barcelona, Spain) with food and tap water available ...

This study assessed salt sensitivity, analyzing the effects of an increased saline intake on hemodynamic, morphological, and oxidative stress and renal variables in experimental thyroid disorders. Six groups of male Wistar rats were used: control, hypothyroid, hyperthyroid, and the same groups treated with salt (8% via food intake). Body weight, blood pressure (BP), and heart rate (HR) were recorded weekly for 6 wk. Finally, BP and HR were recorded directly, and morphological, metabolic, plasma, and renal variables were measured. High-salt intake increased BP in thyroxine-treated rats but not in control or hypothyroid rats. High-salt intake increased cardiac mass in all groups, with a greater increase in hyperthyroid rats. Urinary isoprostanes and H 2O2 were higher in hyperthyroid rats and were augmented by high-salt intake in all groups, especially in hyperthyroid rats. High-salt intake reduced plasma thyroid hormone levels in hyperthyroid rats. Proteinuria was increased in hyperthyroid rats and aggravated by high-salt intake. Urinary levels of aminopeptidases (glutamyl-, alanyl-, aspartyl-, and cystinylaminopeptidase) were increased in hyperthyroid rats. All aminopeptidases were increased by salt intake in hyperthyroid rats but not in hypothyroid rats. In summary, hyperthyroid rats have enhanced salt sensitivity, and high-salt intake produces increased BP, cardiac hypertrophy, oxidative stress, and signs of renal injury. In contrast, hypothyroid rats are resistant to salt-induced BP elevation and renal injury signs. Urinary aminopeptidases are suitable biomarkers of renal injury. salt intake; hyperthyroidism; hypothyroidism; aminopeptidases; blood pressure RENAL FUNCTION AND SALT AND water metabolism can be considerably impaired by thyroid disorders (3, 46). Some authors reported that hypothyroid rats have a lesser ability to concentrate urine and show increased natriuresis after salt or water loading (10,18,25,39) and have a reduced capacity to conserve sodium, which produces a negative sodium balance and death when subjected to dietary sodium restriction (13). However, our group did not observe increased sodium excretion in hypothyroid methimazole-treated rats under some of the above conditions (44) or in pressure-diuresis-natriuresis studies (43). On the other hand, thyroxine (T 4 )-treated rats showed changes in renal hemodynamics and sodium resorption (46), increased blood volume (34), polydipsia/polyuria (15), reduced ability to excrete sodium after hypertonic saline loading (44), and a blunted pressure-diuresis-natriuresis response (43).These data indicate that thyroid disorders are accompanied by major changes in renal sodium handling.Hypothyroidism reduces blood pressure (BP) and prevents experimental hypertension (46), whereas T 4 administration to rats increases BP (6) and accelerates the course of hypertension (46). Although numerous systems can influence BP over the short term, long-term BP regulation depends on the renal excretion of sodium (22). An increased BP in response to dietary sodium (sal...

The effects of clofibrate on the hemodynamic and renal manifestations of increased saline intake were analyzed. Four groups of male Wistar rats were treated for five weeks: control, clofibrate (240 mg/kg/day), salt (2% via drinking water), and salt + clofibrate. Body weight, systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, SBP, HR, and morphologic, metabolic, plasma, and renal variables were measured. Salt increased SBP, HR, urinary isoprostanes, NOx, ET, vasopressin and proteinuria and reduced plasma free T4 (FT4) and tissue FT4 and FT3 versus control rats. Clofibrate prevented the increase in SBP produced by salt administration, reduced the sodium balance, and further reduced plasma and tissue thyroid hormone levels. However, clofibrate did not modify the relative cardiac mass, NOx, urinary ET, and vasopressin of saline-loaded rats. In conclusion, chronic clofibrate administration prevented the blood pressure elevation of salt-loaded rats by decreasing sodium balance and reducing thyroid hormone levels.