CROSS-TOLERANCE BETWEEN ENDOGENOUS NITRIC-OXIDE AND EXOGENOUS NITRIC-OXIDE DONORS

It is still unclear whether cross-tolerance develops between endogenou sly produced nitric oxide and exogenous nitric oxide donors. Thus, cGM P accumulation was determined in cultured aortic smooth muscle cells e xposed to a nitric oxide source. Exposure of human, rat, rabbit, porci ne or bovine smooth muscle cells to sodium nitroprusside led to a time - and concentration-dependent development of tolerance. In rat aortic smooth muscle cells, cross-tolerance developed between the sodium nitr oprusside and S-nitroso-N-acetylpenicillamine, but not between sodium nitroprusside and atriopeptin. In addition, when rat aortic smooth mus cle cells were treated with endotoxin or interleukin-1 beta, they disp layed lower sodium nitroprusside-indused cGMP accumulation as compared to control cells. When rat aortic smooth muscle cells were exposed to sodium nitroprusside for 12 h they displayed a decreased ability to a ccumulate cGMP in response to endothelium-derived nitric oxide release d from bovine aortic endothelial cells. In addition, co-cultures of ra t aortic smooth muscle cells with bovine aortic endothelial cells show ed an L-nitroarginine methylester-sensitive decrease in sodium nitropr usside-induced cGMP accumulation compared to single rat aortic smooth muscle cell cultures. Wt conclude that cross-tolerance between endothe lium-derived nitric oxide and exogenously applied nitric oxide donors occurs in vitro. (C) 1998 Elsevier Science B.V.