Comparison of the pharmacological properties of EDHF-mediated vasorelaxation in guinea-pig cerebral and mesenteric resistance vessels

1 In the presence of L-NNA (100 mu M), indomethacin (10 mu M) and ODQ (10 m u M), acetylcholine induced a concentration-dependent vasorelaxation of gui nea-pig mesenteric and middle cerebral arteries precontracted with cirazoli ne or histamine, but not with high K+, indicating the contribution of an en dothelium-derived hyperpolarizing factor (EDHF). 2 In cerebral arteries, charybdotoxin (ChTX; 0.1 mu M) completely inhibited the indomethacin, L-NNA and ODQ-insensitive relaxation; iberiotoxin (IbTX, 0.1 mu M), 4-aminopyridine (4-AP, 1 mM), or barium (30 mu M) significantly reduced the response; in the mesenteric artery, ChTX and IbTX also reduced this relaxation. Glibenclamide (10 mu M) had no affect in either the mesen teric or cerebral artery. 3 Neither clotrimazole (1 mu M) nor 7-ethoxyresorufin (3 mu M) affected EDH F-mediated relaxation in the mesenteric artery, but abolished or attenuated EDHF-mediated relaxations in the cerebral artery. AM404 (30 mu M), a selec tive anandamide transport inhibitor, did not affect the vasorelaxation resp onse to acetylcholine in the cerebral artery, but in the mesenteric artery potentiated the vasorelaxation response to acetylcholine in an IbTX, and ap amin-sensitive, but SR 141816A-insensitive manner. Ouabain (100 mu M) almos t abolished EDHF-mediated relaxation in the mesenteric artery, but enhanced the relaxation in the cerebral artery whereas the addition of K+ (5-20 mM) to precontracted guinea-pig cerebral or mesenteric artery induced further vasoconstriction. 4 These data suggest that in the guinea-pig mesenteric and cerebral arterie s different EDHFs mediate acetylcholine-induced relaxation, however, EDHF i s unlikely to be mediated by K+.