Vascular bed heterogeneity in age-related endothelial dysfunction with respect to NO and eicosanoids

1 Endothelial dysfunction has been described with ageing but the mechanisms responsible have not been clearly elucidated and might be different from o ne vessel to the other. This study assesses the relative contribution of en dothelial nitric oxide (NO) and cyclo-oxygenase (COX) metabolites in relaxa tion to acetylcholine with ageing in the aorta and the small mesenteric art ery of the rat. 2 In the aorta and branch II or III of superior mesenteric artery (SMA), en dothelium-dependent relaxation to acetylcholine was not different between 1 2-14 (adult) and 32-week-old rats whereas it was reduced at 70-100 (old) we eks of age. 3 Despite an increased endothelial NO-synthase protein expression, the NO-s ynthase inhibitor, NG-nitro-L-arginine-sensitive component of relaxation de creased with ageing. 4 In old rats, exposure to the COX inhibitor, indomethacin, but not the sel ective COX-2 inhibitor, NS-398, potentiated response to acetylcholine. The thromboxane A(2)/prostaglandin H-2 receptor antagonist, GR 32191B enhanced relaxation to acetylcholine in aorta but it had no effect in SMA. Furthermo re, acetylcholine increased thromboxane B-2, production (enzymeimmunoassay) in aorta but not in SMA. Finally, Western blot analysis showed enhanced ex pression of COX-I and 2 in the two arteries with ageing. 5 These results suggest that the decrease in acetylcholine-induced relaxati on with ageing involves reduced NO-mediated dilatation and increased genera tion of vasoconstrictor prostanoids most likely from COX-1. They also point out vascular bed heterogeneity related to the nature of prostanoids involv ed between the aorta (i.e., thromboxane Aa) and the SMA (unidentified) arte ries even though increased expression of COX occurs in both vessels.