QUANTITATIVE CHANGES IN PHARMACODYNAMIC PARAMETERS OF NORADRENALINE IN DIFFERENT RAT AORTA PREPARATIONS - INFLUENCE OF ENDOGENOUS EDRF

1 The aim of the present study was to assess the role of endothelial c ells in the modulation of vasocontractile responses to noradrenaline i n rat isolated aorta when cut as standard helical strips or as ring se gments. 2 Noradrenaline-potency in helical strip preparations evaluate d as -logEC50 was greater than that obtained in endothelium-intact rin g preparations (9.45 +/- 0.28 versus 8.69 +/- 0.09, respectively) (P < 0.05). The maximum contractile response of helical strips was signifi cantly higher than the response of ring preparations (P < 0.05). 3 Sub sequent experiments were performed on helical strips and ring preparat ions where the endothelium was removed by rubbing the luminal surface of the aorta with filter paper. Removal of the endothelium potentiated the noradrenaline-induced contraction in ring preparations, but not i n the helical strips. 4 The nitric oxide synthase inhibitors L-NAME (3 x 10(-5)-3 x 10(-4) M) or L-NNA (1 x 10(4)-3 x 10(-4) M) which were a dded to the tissue bath potentiated the noradrenaline-induced contract ion in the endothelium-intact ring preparations, although only L-NNA i nduced a statistically significant potentiation. Both L-NAME and L-NNA had no effect on the noradrenaline-contraction induced in rings witho ut endothelium, or in helical strips with or without endothelium. 5 Va scular acetylcholine-induced relaxation is dependent on endothelium de rived relaxing factor (nitric oxide). Acetylcholine (10(-9)-10(-6) M) induced a concentration-dependent relaxation in noradrenaline preconst ricted intact rings. The relaxant response was strongly reduced by L-N AME (3 x 10(-5)-1 x 10(-4) M). The relaxant response to acetylcholine was very weak in ring and helical strip preparations without endotheli um, but also, surprisingly, in unrubbed standard helical strips. 6 The present results suggest that the endothelium of standard helical stri p preparations may be greatly damaged, a view confirmed by morphologic al studies. The structural and functional damage of the endothelium in duced very important changes in pharmacodynamic parameters such as in the potency and the maximal responses of vascular preparations to nora drenaline. Therefore, caution must be observed when the potency and in trinsic activity of agonists evaluated on different preparations are c ompared, even if these come from the same vascular segment.