Effects of chronic and acute aminoguanidine treatment on tail artery vasomotion in ageing rats

1 This study was designed to evaluate the effects of aminoguanidine, a selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS), on the reactivity and intracellular calcium ([Ca2+](i)) mobilization induced by noradrenaline in the perfused tail artery from aged WAG/Rij rats. Global mean internal diameter was 350 +/- 15 microns and wail thickness 161 +/- 3 microns. The influence of the endothelium on these responses was also analysed. The intracellular dye fura-2 for [Ca2+](i) measurements was used. 2 Noradrenaline-induced vasoconstriction decreased progressively from 3 to 20 and 30 months. Removal of the endothelium attenuated vasoconstriction in 20 and 30 month-old rats (P<0.05) but not in young rats. 3 Chronic administration of aminoguanidine (50 mg kg(-1) day(-1), p.o.) to WAG/Rij rats from 20 to 30 months enhanced (P < 0.01) the [Ca2+](i)-sensitivity of noradrenaline-induced vasoconstriction. 4 Aminoguanidine (300 muM) in vitro significantly shifted the concentration-vasoconstriction curve to noradrenaline to the left (P < 0.01) in denuded vessels from both 20 and 30 month-old rats. The acute inhibitory effect of aminoguanidine was also observed after chronic aminoguanidine treatment. Aminoguanidine failed to modify vasoconstriction in the presence of the endothelium. 5 Acute aminoguanidine (300 <mu>M) treatment did not modify vasoconstriction induced by noradrenaline in young rats. 6 Quantification of iNOS mRNA expression in tail arteries from 3 and 20 month-old WAG/Rij rats showed that expression was enhanced (x 2.1, P < 0.01) with age. 7 These results suggest that an inflammatory process develops in the media of the rat tail artery with age and that the subsequent increase in non-endothelial iNOS activity attenuates noradrenaline-induced vasoconstriction.