Hypoxia, metabolic inhibition, and isolated rat mesenteric tone: influence of arterial diameter.

The present study examined and compared the effects of severe hypoxia (induced by either substitution of O(2) in the gassing medium with N(2) or by addition of the O(2) scavenger sodium dithionite) and metabolic inhibition (induced by addition of sodium cyanide) on the tone of isolated rat mesenteric resistance vessels. The influence of vessel diameter and the endothelium on responses to these maneuvers was investigated. Hypoxia (due to both substitution of O(2) with N(2) and by addition of 2 mM sodium dithionite) caused near maximal relaxation of all tissues studied. Addition of 10 mM dithionite, however, produced a significantly smaller response. Two mM cyanide also relaxed mesenteric arteries. In small vessels a near maximal relaxation to cyanide was observed, however, in larger vessels the relaxation to metabolic inhibition was significantly less than that observed to hypoxia. Increasing the concentration of cyanide had no further effect on responses. All responses were found to be endothelium-independent. Thus, as the effects of hypoxia and cyanide are not always similar, care must be taken when extrapolating the effects of metabolic inhibition to those of hypoxia. The results of this study suggest that, in large mesenteric vessels at least, an "O(2) sensing step," in addition to effects of metabolism, may be involved in the hypoxic response. Copyright 2000 Academic Press.