title: Cross-tolerance between endogenous nitric oxide and exogenous nitric oxide donors.
abstract: It is still unclear whether cross-tolerance develops between endogenously produced nitric oxide and exogenous nitric oxide donors. Thus, cGMP accumulation was determined in cultured aortic smooth muscle cells exposed to a nitric oxide source. Exposure of human, rat, rabbit, porcine 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 nitroprusside and S-nitroso-N-acetylpenicillamine, but not between sodium nitroprusside and atriopeptin. In addition, when rat aortic smooth muscle cells were treated with endotoxin or interleukin-1beta, they displayed lower sodium nitroprusside-induced 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 accumulate cGMP in response to endothelium-derived nitric oxide released from bovine aortic endothelial cells. In addition, co-cultures of rat aortic smooth muscle cells with bovine aortic endothelial cells showed an L-nitroarginine methylester-sensitive decrease in sodium nitroprusside-induced cGMP accumulation compared to single rat aortic smooth muscle cell cultures. We conclude that cross-tolerance between endothelium-derived nitric oxide and exogenously applied nitric oxide donors occurs in vitro.
authors.affiliation: Vascular Biology Center and Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912-2500, USA.
authors.forename: A
authors.initials: A
authors.lastname: Papapetropoulos
authors.forename: N
authors.initials: N
authors.lastname: Marczin
authors.forename: J D
authors.initials: JD
authors.lastname: Catravas
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects; D002417:Cattle; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D004361:Drug Tolerance; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D013552:Swine
chemical_list: C110881:S-nitro-N-acetylpenicillamine; D009599:Nitroprusside; D009569:Nitric Oxide; D010396:Penicillamine; D006152:Cyclic GMP