Paradoxical cholinergic and purinergic vascular reactivity of rabbit thoracic aorta cold-stored in University of Wisconsin solution

Endothelial dysfunction has been reported in donor blood vessels destined f or organ transplantation following cold-storage preservation with Universit y of Wisconsin solution (UW). This was investigated in the present work. Se gments of rabbit thoracic aorta were mounted on isometric fine-wire myograp hs at 37 degrees C and gassed with 95% O-2/5% CO2, Concentration-dependent vasodilatations to acetylcholine and adenosine-5'-triphosphate (ATP) were o btained in freshly-harvested rabbit aortic rings, with and without the endo thelium, and after 8 days of cold-storage, at 4 degrees C, in either UW, Kr ebs-Bulbring buffer (KBB) or saline, The action of the nitric oxide synthas e inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) (100 mu M) was evalu ated upon the concentration-response curves to determine whether nitric oxi de (NO) exerted any modulatory actions. Endothelium-dependent, NO-mediated responses to acetylcholine were unaltere d after eight days of storage in UW, reduced after storage in KBB and absen t after removal of the vascular endothelium, saline storage or after testin g in the presence of L-NAME, suggesting improved NO-mediated endothelial fu nction with the use of UW. Structural preservation was also confirmed using scanning electron microscopy. In contrast, endothelium-dependent responses to ATP were unchanged after eight days of storage in KBB but were reduced after storage in UW and saline, suggesting purinergic (ATP) endothelial dys function after storage in UW, L-NAME markedly reduced vasodilatation to ATP in freshly harvested rings and after eight days of storage in KBB. This re duction was statistically significant (P < 0.05, Student's two tailed, unpa ired t-test) at -log (M) ATP concentrations of 5.5, 5.0, 4.5, 4.0 and 3.5. NO-dependent vasodilatation to ATP was not attenuated by L-NAME in UW-store d rings. Eight days' UW-storage of rabbit thoracic aortic rings appeared to have differential and paradoxical effects upon NO-dependent vasodilatation to acetylcholine and ATP. Morphological observations using electron microscopy suggested that UW pres erved the vascular endothelium and this was verified by retained vascular r eactivity of endothelium-dependent vasodilatations to acetylcholine. UW-sto rage however, significantly reduced endothelium-dependent relaxation to ATP thereby suggesting that P-2Y-purinoceptors, which are located on the vascu lar endothelium, may be more susceptible to biodegradation than cholinergic receptors and may be responsible for endothelial dysfunction following tra nsplantation.