This study evaluated the action of pomegranate juice (PJ) and its five principal phenolic constituents on rat corpus cavernosum smooth muscle (CCSM). Isometric tension studies were performed after precontraction with phenylephrine in CCSM from rats. Relaxant responses to PJ and its constituents ellagic acid (EA), chlorogenic acid, caffeic acid, cumaric acid and rutin were investigated. PJ and EA caused CCSM relaxations (94.1 +/- 3.7 and 51.3 +/- 9.9%), while others induced limited relaxant responses. EA response was not inhibited by L-N(G)-nitroarginine methyl ester (100 mu M) and 1H-[1,2,4]-oxadiazolo[4,3-a] quinoxalin-1-one (1 mu M). Tetraethylammonium (100 mu M) and apamin (10 mu M) and nifedipine (10 mu M) inhibited EA-induced relaxations at 10(-3) M by 84%, 82% and 78%, respectively. Glibenclamide (10 mu M) inhibited EA response (97%, 100 mu M). PJ-induced relaxation was not altered by several inhibitors. EA was estimated to be responsible for 13.3% of relaxation caused by PJ. Our study demonstrated that PJ and EA-induced marked relaxations in CCSM. The opening of Ca(2 + )-activated K + channels and the inhibition of Ca(2 + )-channels regulate the relaxation by EA, but not PJ. EA has a minor contribution to the marked relaxation obtained by PJ, suggesting the presence of other PJ constituents, which induce nitric oxide-independent corporal relaxation. Further studies are needed to examine the potential of PJ in combination with a PDE5 inhibitor in ED.