HYPOXIC VASODILATION DOES NOT REQUIRE NITRIC-OXIDE (EDRF NO) SYNTHESIS/

Our question was whether inhibition of nitric oxide [endothelium-deriv ed relaxing factor (EDRF)/NO] production in an in situ vascularly isol ated by innervated canine hindlimb would prevent hypoxic vasodilation or interfere with O-2 extraction during ischemic (IH) or hypoxic hypox ia (HH). After a control period, we gave N-G-nitro-L-arginine methyl e ster (L-NAME, 20 mg/kg iv) to two of four groups of six dogs before a 30-min period of IH or HH. In IH, arterial inflow from a pump-membrane oxygenator system was lowered from 65 to 35 ml.min(-1).kg(-1) with PO 2 maintained at similar to 110 Torr. In HH, PO2 was lowered from 107 t o 28 Torr with flow at 78 ml.min(-1).kg(-1). Total O-2 delivery was lo wered to similar to 5 ml.min(-1).kg(-1) in all groups during hypoxia. Hindlimb vascular resistance (LVR) increased from 1.11 +/- 0.09 to 2.2 1 +/- 0.25 peripheral resistance units (PRU;P<0.05) after L-NAME infus ion and hindlimb O-2 uptake increased from 3.9 +/- 0.02 to 4.5 +/- 0.3 ml.min(-1).kg(-1) (P<0.05). In controls, LVR decreased from 1.10 +/- 0.06 to 0.63 +/- 0.04 PRU with HH (P<0.05) and from 1.03 +/- 0.06 to 0 .82 +/- 0.02 PRU (P = NS) with IH. In L-NAME-treated dogs, LVR decreas ed from 2.38 +/- 0.37 to 1.07 +/- 0.13 PRU with HH (P<0.05) and from 2 .04 +/- 0.29 to 1.41 +/- 0.13 PRU (P = NS) with IH. There were no diff erences in O-2 extraction ratio (0.72) or in O-2 uptake between groups during hypoxia. In canine skeletal muscle, blockade of EDRF/NO synthe sis does not appear to affect the vasodilation or the increase in O-2 extraction ratio that occurs with HH or IH. Another source of hypoxic vasodilation must be sought as well as an explantation for the rise in O-2 after L-NAME infusion.