alpha(2)-adrenoceptor antagonists evoke endothelium-dependent and -independent relaxations in the isolated rat aorta

This study was designed to determine whether the alpha(2)-adrennceptor anta gonists idazoxan, yohimbine, and rauwolscine cause endothelium-dependent an d -independent responses in the rat aorta. Rings of rat aorta, with and wit hout endothelium, were suspended for the measurement of isometric force in modified Krebs-Ringer bicarbonate solution (37 degrees C; aerated with 95% O-2 and 5% CO2). The alpha(2)-aadeenocettor antagonists, in the concentrati on range of 10(-8)-10(-6) M, relaxed phenylephrine-contracted rings with, b ut not those without endothelium. alpha(2)-Adrenoceptor antagonists (3 x 10 (-6) M for 1 min) increased the accumulation of cyclic guanosine monophosph ate (cGMP) about twofold in the aortas with endothelium. The relaxation and the increased cGMP induced by alpha(2)-antagonists were attenuated by meth ylene blue (10(-6) M) and N-G-nitro-L-arginine (L-NA, 3 x 10(-5) M), wherea s propranolol (10(-6) M) did not affect the relaxation. In concentrations > 10(-6) M, a, adrenoceptor antagonists relaxed the rat aorta without endothe lium. The endothelium-independent relaxation by andrenoceptor antagonists w as abolished by increased external K+ and reduced significantly by tetraeth ylammonium (TEA, 10(-2) M, a Ca2+-dependent K+ channel blocker), but not in hibited by glibenclamide (10(-5) M, an ATP-scnsitive K+ channel blocker). I n the rabbit aorta, only endothelium-independent relaxations were observed with alpha(2)-andrenoceptor antagonists in the concentration range of 10(-8 )-10(-5) M, and these relaxations were not antagonized by TEA. These result s suggest that alpha(2)-adrenoceptor antagonists relax the rat aorta throug h endothelium-dependent mechanism at lower concentrations and endothelium-i ndependent mechanisms at higher concentrations. The endothelium-dependent r elaxations are likely to be mediated by the endothelium-derived relaxing fa ctor (EDRF)/NO pathway because they are associated with the accumulation of cGMP, whereas the endothelium-independent relaxations map be caused by the opening of potassium channels in the vascular smooth muscle.