Interaction of BKCa channel modulators with adrenergic agonists in the rat aorta is influenced by receptor reserve

Our main objective was to study the interaction of BKCa channel modulators with adrenergic agonists UK 14304 and noradrenatine (NA), acting on alpha(1)-adrenoceptors, in the rat aorta and how this is affected by receptor reserve. NA and UK 14304 evoked concentration-dependent contractions of the rat aorta. UK 14304 was a partial agonist relative to NA in this preparation. The BKCa channel blocker tetraethylammonium (TEA, 1 mM) and opener NS 1619 (3 x 10(-5) M) modulated NA- and UK 14304-induced contractions, and were more effective on UK 14304-induced contractions. TEA (1 mM) increased the maximum response to NA and UK 14304 by about 13% and 300%, respectively, while NS 1619 (3 x 10-5 M) reduced the maximum response to UK 14304 by about 81% compared to 31% for noradrenaline. The effect of TEA on the noradrenaline concentration-response curve was increased after treatment of the aorta with phenoxybenzamine (PBZ), an irreversible alpha(1)-adrenoceptor antagonist, to reduce receptor reserve. We concluded that the interaction of BKCa channel modulators with alpha(1)-adrenergic agonists in the rat aorta was influenced by receptor reserve. (C) 2004 Elsevier Inc. All rights reserved.