AHEART June 47/6

Welsh, Donald G., and Steven S. Segal. Role of EDHF in conduction of vasodilation along hamster cheek pouch arterioles in vivo. Am J Physiol Heart Circ Physiol 278: H1832– H1839, 2000.—We tested whether local and conducted responses to ACh depend on factors released from endothelial cells (EC) in cheek pouch arterioles of anesthetized hamsters. ACh was delivered from a micropipette (1 s, 500 nA), while arteriolar diameter (rest, ,40 μm) was monitored at the site of application (local) and at 520 and 1,040 μm upstream (conducted). Under control conditions, ACh elicited local (22–65 μm) and conducted (14–44 μm) vasodilation. Indomethacin (10 μM) had no effect, whereas Nv-nitro-L-arginine (100 μM) reduced local and conducted vasodilation by 5–8% (P , 0.05). Miconazole (10 μM) or 17-octadecynoic acid (17-ODYA; 10 μM) diminished local vasodilation by 15–20% and conducted responses by 50–70% (P , 0.05), suggesting a role for cytochrome P-450 (CYP) metabolites in arteriolar responses to ACh. Membrane potential (Em) was recorded in smooth muscle cells (SMC) and in EC identified with dye labeling. At rest (control Em, typically 230 mV), ACh evoked local (15–32 mV) and conducted (6–31 mV) hyperpolarizations in SMC and EC. Miconazole inhibited SMC and EC hyperpolarization, whereas 17-ODYAinhibited hyperpolarization of SMC but not of EC. Findings indicate that AChinduced release of CYP metabolites from arteriolar EC evoke SMC hyperpolarization that contributes substantively to conducted vasodilation.