ENDOTHELIUM-DEPENDENT VASODILATATION PRODUCED BY THE L-ARGININE NITRIC-OXIDE PATHWAY IN NORMAL AND ISCHEMIC BONE

We used an experimental model of the perfused isolated rabbit tibia to investigate the vasodilatation produced by nitric oxide in the circul ation of bone. Tibiae were perfused at a constant flow rate while the perfusion pressure was monitored continuously. Perfusion pressure was raised by the addition of noradrenaline to the perfusate, and dose res ponses were measured for bolus doses of acetylcholine and sodium nitro prusside. N-omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis, was then added to the perfusate at a conce ntration of 10(-4) M, and the dose responses to acetylcholine and sodi um nitroprusside were repeated. Measurements were performed on groups of bones after 0, 6,12, and 24 hours of normothermic ischemia (n 5, 4, 6, and 9, respectively. Both acetylcholine and sodium nitroprusside p roduced significant Vasodilatation after 0 and 6 hours' ischemia, but no significant response was observed after 12 or 24 hours of ischemia. The vasodilatation produced by acetylcholine was significantly attenu ated when L-NAME was added to the perfusate, but the vasodilatation pr oduced by sodium nitroprusside remained unchanged. These findings conf irm endothelial production of NO by stimulation of muscarinic receptor s on the endothelial cells in bone and indicate that vasodilatation vi a the L-arginine/NO pathway remains viable for 6 hours after normother mic ischemia.