The effect of 131I-induced hypothyroidism on the levels of nitric oxide (NO), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), total nitric oxide synthase (NOS) activity, and expression of NOS isoforms in rats

Accumulating evidence has shown that hypothyroidism affects the cardiovascular system, significantly increasing the incidence of cardiovascular diseases. In the present study we investigated the effect of radioactive iodine (I-131)-induced hypothyroidism on several parameters of vascular function, such as nitric oxide (NO), total nitric oxide synthase (NOS) activity and expression of NOS isoforms, as well as on interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) as indicators of inflammation, in rats. A dose of 150 mu Ci of 131-I was determined as optimal for establishing the model of hypothyroidism in rats. After administration of 131-I, at the end of month 1, 2, and 4 (n = 3 for each time point), NO, IL-6, and TNF-alpha in the serum and total NOS activity in the aorta were determined in 150 mu Ci group, compared to controls. The mRNA and protein expression of endothelial, neuronal, and inducible NOS (eNOS, nNOS, and iNOS) in the rat aorta was also estimated, using quantitative reverse transcription polymerase chain reaction and Western blot, respectively. The levels of IL-6 and TNF-alpha increased in 150 mu Ci group; the results were significant at the end of month 2 and 4 for IL-6, and at all time points for TNF-alpha. The levels of NO decreased significantly at the end of month 2 and 4 in 150 mu Ci group. The total NOS activity increased significantly in 150 mu Ci group, at all three time points. Significant changes in the mRNA and protein expression of all three NOS isoforms were observed in 150 mu Ci group compared to controls. NO, IL-6, TNF-alpha levels and NOS activity and expression are altered in hypothyroid state, and the underlying mechanism should be further investigated.