ANALYSIS OF THE ACTION OF IDAZOXAN CALLS INTO QUESTION THE RELIABILITY OF THE RAT ISOLATED SMALL MESENTERIC-ARTERY ASSAY AS A PREDICTOR FORALPHA(1)-ADRENOCEPTOR-MEDIATED PRESSOR ACTIVITY

We have studied the effects of idazoxan in rat aorta and small mesente ric artery. In the aorta, idazoxan behaved as a partial agonist (pK(A) =6.30). Prazosin produced rightward shift (pA(2)=9.88) and steepening of the idazoxan curve. In contrast, idazoxan had no effect of basal te nsion in the mesenteric artery, but shifted the noradrenaline curve to the right in a parallel manner (pA(2)=6.12). The selective alpha(1)-a drenoceptor agonist, indanidine, also behaved as a partial agonist in the aorta and produced no significant contractions of the small mesent eric artery. Since idazoxan and indanidine have been reported to raise blood pressure in the pithed rat via an action at vascular alpha(1)-a drenoceptors, these results call into question the reliability of the small mesenteric artery assay as a predictor for alpha(1)-adrenoceptor -mediated presser activity in vivo.