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

2000, British Journal of Pharmacology

In the presence of L-NNA (100 mM), indomethacin (10 mM) and ODQ (10 mM), acetylcholine induced a concentration-dependent vasorelaxation of guinea-pig mesenteric and middle cerebral arteries precontracted with cirazoline or histamine, but not with high K + , indicating the contribution of an endothelium-derived hyperpolarizing factor (EDHF). 2 In cerebral arteries, charybdotoxin (ChTX; 0.1 mM) completely inhibited the indomethacin, L-NNA and ODQ-insensitive relaxation; iberiotoxin (IbTX, 0.1 mM), 4-aminopyridine (4-AP, 1 mM), or barium (30 mM) signi®cantly reduced the response; in the mesenteric artery, ChTX and IbTX also reduced this relaxation. Glibenclamide (10 mM) had no aect in either the mesenteric or cerebral artery. 3 Neither clotrimazole (1 mM) nor 7-ethoxyresoru®n (3 mM) aected EDHF-mediated relaxation in the mesenteric artery, but abolished or attenuated EDHF-mediated relaxations in the cerebral artery. AM404 (30 mM), a selective anandamide transport inhibitor, did not aect the vasorelaxation response to acetylcholine in the cerebral artery, but in the mesenteric artery potentiated the vasorelaxation response to acetylcholine in an IbTX, and apamin-sensitive, but SR 141816Ainsensitive manner. Ouabain (100 mM) almost 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 arteries dierent EDHFs mediate acetylcholine-induced relaxation, however, EDHF is unlikely to be mediated by K + .