Treatment with the Nitric Oxide Donor SNP Increases Triiodothyronine Levels in Hyper- and Hypothyroid Sprague-Dawley Rats

Abstract

Nitric oxide pathway might play a crucial role in the pathophysiology of thyroid dysfunctions. This study aimed to investigate the impact of nitric oxide (NO) on hypothyroid and hyperthyroid Sprague-Dawley rats under controlled diet. Furthermore, the effects of the nitric oxide donor sodium nitroprusside (SNP) on thyroid dysfunctions were also assessed. Sprague-Dawley rats (n=107) were subdivided into normal diet and high-fat diet (HFD) groups and grouped into controls, hypothyroid, hyperthyroid, and SNP treated groups. Hypothyroidism was induced through propylthiouracil, whereas hyperthyroidism by triiodothyronine (T3). After 12 weeks of T3 treatment, serum nitric oxides (NOX), endogenous asymmetric dimethylarginine (ADMA), body weight and food intake were analyzed. Hypothyroid rats showed decreased serum T3 levels, hyperthyroid rats increased T3 compared to controls. Diet had no impact on T3. Thyroid dysfunctions were accompanied by changes in calorie intake and body weight. Serum NOX was significantly reduced in normal diet hypothyroid rats. SNP administration compensated the decrease and markedly increased T3. NO synthase inhibitor ADMA levels were significantly higher in the HFD control group than in the normal diet controls. ADMA was declined in both hypothyroid groups and increased in normal diet hyperthyroid rats. An association of thyroid dysfunctions with reduced bioavailability of NO and alterations of ADMA levels could be established. Treatment with the NO donor SNP resulted in an increase of serum T3 levels. These results demonstrate that the NO pathway is implicated in thyroid dysfunctions, which may be of clinical relevance.

Oxidized LDL Is Strictly Limited to Hyperthyroidism Irrespective of Fat Feeding in Female Sprague Dawley Rats

“…This may be explained by the fact that in rats experimental hypothyroidism induces cretinism as described in detail elsewhere [19]. Cretinism causes growth retardation and a strongly reduced metabolic rate which may be responsible for the different findings.…”

“…To avoid such side effects in this study, dose and duration of treatment were based on previous studies where the treatment was well tolerated [19,20,21,22]. …”

“…Groups 1–3 were fed a normal rodent diet, whereas groups 4–6 were fed with a HFD. Hypothyroidism was induced via administration of 6-propylthiouracil (0.04 g/100 mL) into the tap drinking water over the whole experimental period of 12 weeks as described [19,20,21]. Hyperthyroidism was induced with 3,3',5-triiodothyronine (T3) (300 μg/kg in 0.50 mM NaOH) via intraperitoneal (i.p.)…”

Neonatal hypothyroidism does not increase Sertoli cell proliferation in iNOS−/− mice

“…Both hypothyroidism and low levels of nitric oxide cause hypertension and heart failure, and are involved in vasodilation and endothelial cells secretion (Grieve et al 1999, Taddei et al 2003, McAllister et al 2005a,b, Virdis et al 2009. It was also shown in the literature that hypothyroidism causes reduction in the nitric oxide levels, and this can be compensated by sodium nitroprusside (SNP), a NO donor compound (Rodríguez-Arnao et al 2003, Ragginer et al 2013. Thus, it can be hypothesized that a redundant mechanism occurs in the testis when we associate hypothyroidism with iNOS deficiency, an interesting and intriguing hypothesis that still needs to be investigated.…”

Hypothyroidism Exacerbates Thrombophilia in Female Rats Fed with a High Fat Diet

“…Regarding body weight changes in various groups it has to be mentioned that findings in rats cannot be transferred to patients with thyroid dysfunctions, as described in detail [ 17 ]. The main reason is the declined development and growth of hypothyroid rats, due to missing appropriate thyroid hormones for growth, and on the other hand the increased metabolic rate in hyperthyroid rats, which results in decreased body weight.…”