Basal and induced nitric oxide and cGMP productions are decreased in senescent cultured rat articular chondrocytes

The effects of interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and lipopolysaccharide (LPS) on the productions of nitric oxide (NO) and cGMP by cultured articular chondrocyte (AC) monolayers from 1-, 8- and 18-month old male Wistar rats were studied. It was found that basal NO and cGMP productions decrease with the age of animals. The productions were more than 2-fold greater in cells from 1-month old rats then in cells from older animals. IL-1, TNF-alpha, and LPS stimulated all three types of cells to produce NO and cGMP in a time- and concentration-dependent manner. Although the cells from young animals produced more NO per mu g DNA, the older counterparts were more sensitive to these agents since they produced more NO upon stimulation then the corresponding non-stimulated controls. At the concentration of 10(-3) M, the nitric oxide synthase (NOS) inhibitor, N-g-monomethyl-L-arginine (L-NMA), blocked, although incompletely, both the basal and stimulated NO and cGMP productions in cells from the 1 and 8-month old rats and only induced productions in 18-month old counterparts. These results show a decreased capacity of unstimulated-and stimulated-AC from old rats to produce NO and cGMP in culture, which may affect the ageing cells in some yet unknown way. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.