Article date: November 1991
By: Michael D. Randall, Tudor M. Griffith, in Volume 104, Issue 3, pages 743-749
An isolated, buffer‐perfused rabbit ear preparation was used to investigate the influence of NG‐nitro‐l‐arginine methyl ester (l‐NAME) on endothelium‐dependent vasodilatation and modulation of vasoconstrictor responses and vascular conductance.
Acetylcholine (0.55 pmol‐1.6 nmol) caused dose‐related vasodilatation of preparations constricted by the combination of 5‐hydroxytryptamine and histamine (both 1 μm), with an ED50 = 31.1 ± 7.8 pmol and a maximum dilatation of 69.9 ± 4.3%. In the presence of 10 μm l‐NAME the dose‐response for vasodilator effects was shifted significantly (P < 0.001) to the right (ED50 = 3.07 ± 1.18 nmol) and there was a significant (P < 0.01) depression of the maximum response (Rmax = 44.3 ± 4.0%). The higher concentration of 100 μm l‐NAME completely abolished vasodilatation to acetylcholine. l‐Arginine (10 mm) did not reverse the inhibitory actions of l‐NAME at either concentration.
l‐NAME 100 μm, augmented vascular tone induced by 1 μm 5‐hydroxytryptamine and 1 μm histamine, thus altering the characteristics of both pressure/flow and conductance/flow relationships such that conductance was reduced at all flow rates. The augmentation of constrictor tone was reversed in a concentration‐dependent manner by l‐arginine (10 μm–10 mm) and the effect of l‐NAME on the conductance/flow relationships was similarly reversed by 10 mm l‐arginine. The augmentation of tone was endothelium‐dependent as it did not occur following functional destruction of the endothelium by perfusion of the vascular bed with the detergent CHAPS (0.3%) for 150 s.
In conclusion, l‐NAME is a potent inhibitor of agonist‐induced endothelium‐dependent vasodilatation. l‐NAME reduces vascular conductance in pharmacologically constricted preparations and this emphasizes the important role of EDRF in vascular regulation. The ability of l‐arginine to reverse l‐NAME‐induced inhibition of basal EDRF activity but not l‐NAME‐induced inhibition of agonist‐induced endothelium‐dependent relaxations suggests that there is pharmacological heterogeneity in the mechanisms responsible for the conversion of l‐arginine to EDRF.
An isolated, buffer‐perfused rabbit ear preparation was used to investigate the influence of NG‐nitro‐l‐arginine methyl ester (l‐NAME) on endothelium‐dependent vasodilatation and modulation of vasoconstrictor responses and vascular conductance.
Acetylcholine (0.55 pmol‐1.6 nmol) caused dose‐related vasodilatation of preparations constricted by the combination of 5‐hydroxytryptamine and histamine (both 1 μm), with an ED50 = 31.1 ± 7.8 pmol and a maximum dilatation of 69.9 ± 4.3%. In the presence of 10 μm l‐NAME the dose‐response for vasodilator effects was shifted significantly (P < 0.001) to the right (ED50 = 3.07 ± 1.18 nmol) and there was a significant (P < 0.01) depression of the maximum response (Rmax = 44.3 ± 4.0%). The higher concentration of 100 μm l‐NAME completely abolished vasodilatation to acetylcholine. l‐Arginine (10 mm) did not reverse the inhibitory actions of l‐NAME at either concentration.
l‐NAME 100 μm, augmented vascular tone induced by 1 μm 5‐hydroxytryptamine and 1 μm histamine, thus altering the characteristics of both pressure/flow and conductance/flow relationships such that conductance was reduced at all flow rates. The augmentation of constrictor tone was reversed in a concentration‐dependent manner by l‐arginine (10 μm–10 mm) and the effect of l‐NAME on the conductance/flow relationships was similarly reversed by 10 mm l‐arginine. The augmentation of tone was endothelium‐dependent as it did not occur following functional destruction of the endothelium by perfusion of the vascular bed with the detergent CHAPS (0.3%) for 150 s.
In conclusion, l‐NAME is a potent inhibitor of agonist‐induced endothelium‐dependent vasodilatation. l‐NAME reduces vascular conductance in pharmacologically constricted preparations and this emphasizes the important role of EDRF in vascular regulation. The ability of l‐arginine to reverse l‐NAME‐induced inhibition of basal EDRF activity but not l‐NAME‐induced inhibition of agonist‐induced endothelium‐dependent relaxations suggests that there is pharmacological heterogeneity in the mechanisms responsible for the conversion of l‐arginine to EDRF.
DOI: 10.1111/j.1476-5381.1991.tb12498.x
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