Thyrocyte release of asymmetric dimethylarginine does not account for human thyrocyte inhibition of endothelial cell cyclic GMP

Background: The thyroid gland produces and responds to the signalling molec ule nitric oxide (NO). The activity of NO synthase (NOS) may be regulated b y endogenous NOS inhibitors such as asymmetric dimethylarginine (ADMA). Objective: To investigate whether human thyrocytes are capable of regulatin g NOS activity via the production of ADMA. Design: Human thyrocytes were incubated with human umbilical vein endotheli al cells (HUVEC) in order to determine the effect on HUVEC NOS activity. HU VEC cGMP production over a 3-h period was measured as an indicator of NOS a ctivity in the absence and presence of thyrocytes. To determine thyrocyte p roduction of ADMA, samples of conditioned media were analysed by HPLC. Results: The presence of primary human thyrocytes or immortalized human thy rocyte SGHTL-189 cells caused a significant inhibition of both basal (appro ximately 57% inhibition) and thrombinstimulated (approximately 42% inhibiti on) HUVEC cGMP production. Both primary human thyrocytes and SGHTL-189 cell s released ADMA (approximately 0.28 mu g per 10(6) thyrocytes over a 3-day period). However, excess L-arginine, the natural substrate for NOS, was una ble to overcome thyrocyte inhibition of HUVEC cGMP production. Conclusion: These data indicate that human thyrocytes potently reduce endot helial cell cGMP concentrations, and that thyrocytes produce the endogenous NOS inhibitor, ADMA. However, the inhibition of endothelial cGMP is not me diated via thyrocyte production of a competitive NOS inhibitor.