Experimental arthritis is an animal model of chronic inflammation that is associated with growth inhibition and a decrease in pituitary growth hormone (GH) secretion. Nitric oxide (NO) is an important mediator in inflammatory processes. Several studies suggest that NO can mediate the inhibition of pituitary GH secretion during chronic inflammation. For this purpose we administered aminoguanidine, a selective inhibitor of inducible nitric oxide synthase (iNOS), to arthritic rats.

Experimental arthritis was induced by a subcutaneous injection of Freund adjuvant to male Wistar rats. Control rats were injected with paraffin oil. Twenty days after adjuvant injection, arthritic and control animals were divided into two groups; one was treated with aminoguanidine (200 mg kg^-1 S.C. daily, during 8 days), and the second group was injected daily with 250 µl of saline S.C. On day 28 after adjuvant injection, all rats were humanely killed by decapitation and serum concentration of nitrites + nitrates was determined by the Griess method. Hypothalamic somatostatin and pituitary GH gene expression were measured by Northern blot hybridization. Comparison of means was performed with Duncan’s multiple range test.

Aminoguanidine treatment decreased the inflammatory symptoms and the serum concentration of nitrites + nitrates in arthritic rats (P < 0.01). Chronic arthritis induced a significant decrease (P < 0.01) in pituitary GH mRNA, whereas it increased (P < 0.01) the hypothalamic somatostatin mRNA. Aminoguanidine administration did not modify pituitary GH or hypothalamic somatostatin gene expression in control rats. In contrast, aminoguanidine treatment was able to prevent the decrease in pituitary GH mRNA and the increase in hypothalamic somatostatin mRNA in arthritic rats. All these data suggest that the increased released of NO during chronic inflammation plays an inhibitory role in pituitary GH gene expression.

This work was supported by FIS grant 00/0949.