ENDOTHELIUM-DERIVED NITRIC-OXIDE PARTIALLY MEDIATES SALBUTAMOL-INDUCED VASODILATATIONS

This study examined the ability of salbutamol (selective beta(2)-adren oceptor agonist) to cause endothelium-dependent relaxation in rat aort ic rings and depressor response in conscious rats. Salbutamol (0.01-10 0 mu M) concentration dependently relaxed preconstricted aortic rings. The relaxant response was partially attenuated by either mechanical r emoval of the endothelium or treatment with NG-nitro-L-arginine methyl ester (L-NAME, 100 mu M). In conscious rats, either i.v. infused phen ylephrine (5 mu g/kg per min) or i.v. bolus injected L-NAME (12.8 mg/k g), but not the vehicle, caused similar sustained increases in mean ar terial; pressure (MAP). I.v. infused salbutamol (2-128 mu g/kg per min , each dose for 5 min) dose dependently decreased MAP in vehicle-treat ed rats; the depressor responses were potentiated by hypertension indu ced by phenylephrine.. In contrast, the magnitudes of the depressor re sponse to salbutamol in L-NAME-treated rats were less than those in ra ts pretreated with phenylephrine or the vehicle. I.v. bolus injections of salbutamol (0.25-16 mu g/kg) also caused dose-dependent and transi ent decreases in MAP in vehicle-treated rats. The magnitude but not th e duration of the depressor response to salbutamol was less in rats tr eated with L-NAME, compared to those in rats given phenylephrine or th e vehicle. These results suggest that endothelium-derived nitric oxide is partially involved in beta(2)-adrenoceptor-mediated vasodilatation .