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Notes: 1. In order to examine the possible involvement of the endothelium and K+ channel activation in the relaxation induced by dobutamine, a β-adrenoceptor agonist, in rat isolated mesenteric arteries, the effects of inhibitors of nitric oxide (NO) activity, blockers of K+ channels and high extracellular K+ were studied by measuring isometric tension in both endothelium-intact and -denuded arteries.2. Dobutamine inhibited the phenylephrine (PE)-induced sustained tension with a pEC50 of 7.40±0.08 in endothelium-intact arteries. Removal of functional endothelium attenuated the effect of dobutamine. The relaxation induced by dobutamine was inhibited by the β1-adrenoceptor antagonist CGP20712A (3μ.mol/L) but not by the β2-adrenoceptor antagonist ICI 118 551 (3 μmol/L) in endothelium-denuded arteries.3. Pretreatment with NG-nitro-l-arginine (l-NNA; 100 μmol/L) or methylene blue (3 μmol/L) induced a similar degree of inhibition of the dobutamine-induced relaxation in endothelium-intact arteries, while NG-nitro-d -arginine (100 (μmol/L) and indomethacin (10 μmol/L) had no effect. In contrast, pretreatment with L -NNA (100 μmol/L) did not affect the relaxation induced by sodium nitroprusside (SNP) or forskolin. Methylene blue (3μmol/L) inhibited the relaxant response to SNP.4. Charybdotoxin (CTX; 100nmol/L), iberiotoxin (IBX; 100nmol/L) and tetraethylammonium ions (TEA+; 3mmol/L) significantly reduced the dobutamine-induced relaxation. Tetrapentylammonium ions (TPA+; 5μmol/L) markedly inhibited the relaxant effect of dobutamine. The pECso values for control and in the presence of TPA+ in endothelium-intact arteries were 7.35±0.11 and 6.14±0.17, respectively, and 6.35±0.09 and 5.87±0.17 for control and in the presence of TPA+ in endothelium-denuded arteries, respectively. In contrast, glibenclamide (3 μ-mol/L) was ineffective. At 5 μmol/L, TPA+ also inhibited the relaxation induced by forskolin.5. The maximal relaxation of PE-contracted arteries induced by 3μmol/L dobutamine was completely abolished in the 60mmol/L K+-contracted arteries with and without endothelium, while dobutamine at a concentration greater than 3 μmol/L induced inhibition of the high-K+ response.6. The present results indicate that endothelium, probably NO but not prostacyclin, was involved in the dobutamine-induced relaxation in rat mesenteric arteries. Activation of CTX-, IBX- and TPA+-sensitive K+ channels contributed towards the observed relaxation. Loss of the ability to relax the 60 mmol/L K+-contracted arteries suggests that endothelium-derived vasoactive factors affected by concentrations of dobutamine less than 3 μmol/L may also act through K+ channels in our preparations. Higher concentrations of dobutamine may have a direct, endothelium-independent relaxant effect.