NO/PGI2‐independent vasorelaxation and the cytochrome P450 pathway in rabbit carotid artery

摘要: 1 The nature and cellular mechanisms that are responsible for endothelium-dependent relaxations resistant to indomethacin NG-nitro-L-arginine methyl ester (l-NAME) were investigated in phenylephrine (PE) precontracted isolated carotid arteries from the rabbit. 2 In presence of cyclo-oxygenase inhibitor, (10 μm), acetylcholine (ACh) induced a concentration-and relaxation PE-induced tone which was more potent than calcium ionophore A23187 with pD2 values 7.03 ± 0.12 (n = 8) 6.37 6), respectively. The ACh-induced response abolished by removal endothelium, but not altered when omitted (pD2 value 7.00 0.10 maximal 99 3%, n 6). Bradykinin histamine (0.01–100 μm) had no effect either upon resting or 5). 3 In plus NO synthase L-NAME (30 abolished. However, ACh abolished, although it significantly inhibited decreasing 6.48 67 respectively (for both P < 0.01, 8). L-NAME/indomethacin insensitive vasorelaxation completely preconstriction tissues potassium chloride (40 mM, 8). 4 The Ca2+-activated K+ (KCa) channel blockers, tetrabutylammonium (TBA, 1 =5) charybdotoxin (CTX, 0.1 μM, =5), nitric oxide (NO) prostacyclin (PGI2)-independent ACh. iberiotoxin (ITX, μm, apamin (1–3 6) only partially relaxation. 5 Inhibitors cytochrome P450 mono-oxygenase, SKF-525A (1–10 clotrimazole (1 5) 17-octadecynoic acid (17-ODYA, 3 7) also reduced NO/PGI2-independent ACh. 6 In endothelium-denuded rings rabbit arteries, exogenous KCa blockade CTX (0.1 5), mono-oxygenase blockers 4) 5). NO-induced shifted right LY83583 4), guanylyl cyclase 6.95 0.14 6.04 0.09 (P <0.01). 7 ACh concentration-dependent arterial segments sandwiched endothelium-intact donor segments. This largely unaffected indomathacin μM), combination indomethacin, TBA 5). 8 These data suggest artery: (a) can induce release EDHF, whereas evokes (b) diffusible EDHF released may be P450-derived arachidonic metabolite, (c) EDHF-induced involves opening at least two types channels, mediates via guanosine 3′: 5′-cyclic monophosphate (cyclic GMP)-mediated pathway, pathway channels do seem involved.