Pentobarbital-sensitive EDHF comediates ACh-induced arteriolar dilation inthe hamster microcirculation

It is unclear to what extent the endothelium-derived hyperpolarizing factor (EDHF) contributes to the control of microcirculatory blood flow in vivo. We analyzed, by intravital microscopy in hamster muscles, the potential rol e of EDRF along the vascular tree under stimulated (ACh) or basal condition s. Experiments were performed in conscious as well as anesthetized (pentoba rbital, urethan) animals. Additionally, cellular effects of the potential E DHF were studied in isolated small arteries. In pentobarbital-anesthetized animals, treatment with N-omega-nitro-L-arginine. (L-NNA; 30 mu mol/l) and indomethacin (3 mu mol/l) reduced the dilation in response to 10 mu mol/l A Ch from 60 +/- 6 to 20 +/- 4%. This nitric oxide/prostaglandin-independent dilation (NPID), which was of a similar magnitude in large and small arteri oles, was abolished by potassium depolarization or charybdotoxin (ChTX, 1 m u mol/l) but not by glibenclamide. In conscious animals, NPID amounted to 3 3 +/- 3%. The inhibitor of the P-450 monooxygenase 17-octadecynoic acid (OD YA) reduced NPID further to 9 +/- 4%. ChTX abolished the NPID and also redu ced basal diameters (by -11 +/- 3%). The induction of anesthesia with pento barbital reduced NPID (to 12 +/- 6%), whereas urethan anesthesia was withou t effect. Pentobarbital also reduced the ACh-induced hyperpolarization of v ascular smooth muscle ih isolated arteries, whereas ChTX abolished it. This study suggests that a considerable part of the ACI 1 dilation in the micro circulation is mediated by EDHF, which also contributes to the control of b asal tone in conscious animals. The direct inhibitory effect of pentobarbit al and ODYA supports the idea that "microcirculatory" EDHF is a product of the cytochrome P-450 pathway. The role of EDHF might be underestimated in p entobarbital-anesthetized animals.