The effects of candesartan on human AT(1) receptor-expressing Chinese hamster ovary cells

Chinese hamster ovary cells expressing the cloned human angiotensin II rece ptor of the AT(1) subtype (CHO-AT(1) cells) were used as an "in vitro" mode l system to investigate the action mechanism of the nonpeptide AT(1) recept or blocker candesartan. In the presence of 10 mM LiCl, angiotensin II cause s a long-lasting increase in the production of inositol phosphates in these cells. This effect is dose-dependent with half-maximal stimulation (EC50) at 3 nM angiotensin II. Preincubation of the cells for 30 min at 37 degrees C with candesartan decreases the maximal response to angiotensin II by up to 90%, with a half-maximal decrease at 0.5 nM candesartan. At this concent ration, candesartan only produces a slight rightward shift of the angiotens in II dose-response curve. Recovery experiments on CHO-AT(1) cells reveal t hat the inhibitory effect of candesartan is only slowly reversed after remo val of the blocker. The insurmountable effect of candesartan can therefore be ascribed to its long-lasting inhibition of the AT(1) receptor.