ROLE OF THE VASCULAR ENDOTHELIUM IN O-2 EXTRACTION DURING PROGRESSIVE ISCHEMIA IN CANINE SKELETAL-MUSCLE

O-2 uptake (VO2) is defended during decreased O-2 delivery (QO(2)) by an increase in the O-2 extraction ratio (O(2)ER, VO2/O-2), presumably by recruitment of capillaries. This study tested the hypothesis that activity ofthe microvascular endothelium plays a necessary role in achievement of maximal O(2)ER. We pump perfused the vascularly isolated hindlimbs of 24 anesthetized and paralyzed dogs at progressively lower flows over a 90-min period. In eight dogs, hindlimb vascular endothelium was removed by injection of deoxycholate (DOG) into the perfusing artery before the ischemic challenge. DOC treatment resulted in loss of normal in vivo and in vitro endothelium-dependent dilatory responses to acetylcholine, but endothelium-independent vascular smooth muscle responses were intact. Eight other dogs were pretreated with nitro-L-arginine methyl ester plus indomethacin (L + I group) to block the synthesis of the vasodilators nitric oxide and prostacyclin. L + I and DOC treatment were associated with increases in hindlimb vascular resistance of 168 +/- 17 and 63 +/- 12%, respectively. O(2)ER at critical QO(2) (QO(2) at which VO2 begins to decrease) was 81 +/- 2% in eight control dogs, 66 +/- 6% in L + I, and 42 +/- 4% in DOC, indicating a significant O-2 extraction defect in the two treatment groups. These data suggest that products of the vascular endothelium play an important role in the matching of O-2 supply to demand during supply limitation in skeletal muscle.