Salt sensitivity in experimental thyroid disorders in rats

Abstract

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...

Long-Term Consequences of Uninephrectomy in Male and Female Rats

“…Our study clearly demonstrates that aging in female rats and a reduction in nephron number in male or female rats cause salt-sensitive hypertension. Moreover, variables related to salt-induced renal injury, such as proteinuria, N-acetyl-β-d-glucosaminidase, and isoprostanes, 16,29 were markedly increased by the high-salt intake in both UNX groups, indicating that UNX increases renal salt sensitivity.…”

“…Our study clearly demonstrates that aging in female rats and a reduction in nephron number in male or female rats cause salt-sensitive hypertension. Moreover, variables related to salt-induced renal injury, such as proteinuria, N-acetyl-β-d-glucosaminidase, and isoprostanes, 16,29 were markedly increased by the high-salt intake in both UNX groups, indicating that UNX increases renal salt sensitivity.Several studies have extensively detailed morphological changes in the kidney during aging. 30,31 The normal aging process leads to slightly more pronounced changes in kidney morphology in male versus female rats.…”

Dietary salt restriction in hyperthyroid rats. Differential influence on left and right ventricular mass

“…6 Our group recently observed that saline loading increased the ventricular weight (VW) and ventricular-to-body weight (VW/BW) ratio in control, hyperthyroid, and hypothyroid rats and increased the susceptibility of hyperthyroid rats to saline-induced cardiac hypertrophy. 2 The same study found that proteinuria levels were twofold higher in hyperthyroid rats than in controls and that a high salt intake did not change these levels in normal and hypothyroid rats but markedly increased them in hyperthyroid rats. Conversely, salt restriction has been reported to have beneficial effects on cardiac hypertrophy, proteinuria, and BP in normotensive and hypertensive rats.…”

“…2 Cardiac mass can be modulated by sodium concentrations in vitro or dietary sodium intake in vivo. In cultured neonatal rat myocardial myoblasts, cellular protein content and cell size increased with higher sodium concentration in the medium.…”

The renin–angiotensin system in thyroid disorders and its role in cardiovascular and renal manifestations

“…Damaged tubular cells release these enzymes into the ultrafiltrate, thereby increasing their activity in urine. Our group recently investigated urinary aminopeptidase activities as early biomarkers of kidney injury, finding that a higher activity of urinary aminopeptidases precedes the increase in proteinuria in hyperthyroid rats (Perez-Abud et al 2011). Moreover, from a diagnostic standpoint, urinary aminopeptidase values may be suitable predictors of renal injury.…”