Role of EDHF in conduction of vasodilation along hamster cheek pouch arterioles in vivo.
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, approximately 40 microm) was monitored at the site of application (local) and at 520 and 1,040 microm upstream (conducted). Under control conditions, ACh elicited local (22-65 microm) and conducted (14-44 microm) vasodilation. Indomethacin (10 microM) had no effect, whereas N(omega)-nitro-L-arginine (100 microM) reduced local and conducted vasodilation by 5-8% (P < 0.05). Miconazole (10 microM) or 17-octadecynoic acid (17-ODYA; 10 microM) 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 (E(m)) was recorded in smooth muscle cells (SMC) and in EC identified with dye labeling. At rest (control E(m), typically -30 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-ODYA inhibited hyperpolarization of SMC but not of EC. Findings indicate that ACh-induced release of CYP metabolites from arteriolar EC evoke SMC hyperpolarization that contributes substantively to conducted vasodilation.
Welsh
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The John B. Pierce Laboratory and Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06519, USA.
Segal
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D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D001685:Biological Factors / Q000502:physiology*; D002610:Cheek / Q000098:blood supply*; D006224:Cricetinae; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D008825:Miconazole / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D001685:Biological Factors; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; C067410:endothelium-dependent hyperpolarization factor; D019335:Nitroarginine; C047008:17-octadecynoic acid; D008825:Miconazole; D007213:Indomethacin