Role of the vascular endothelium in O2 extraction during progressive ischemia in canine skeletal muscle.
O2 extraction during progressive ischemia in canine skeletal muscle, J. Appl. Physiol. 79(4): 1351-1360, 1995.--O2 uptake (VO2) is defended during decreased O2 delivery (QO2) by an increase in the O2 extraction ratio (O2ER, VO2/QO2), presumably by recruitment of capillaries. This study tested the hypothesis that activity of the microvascular endothelium plays a necessary role in achievement of maximal O2ER. 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 (DOC) 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. O2ER at critical QO2 (QO2 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 O2 extraction defect in the two treatment groups. These data suggest that products of the vascular endothelium play an important role in the matching of O2 supply to demand during supply limitation in skeletal muscle.
Curtis
S E
SE
Department of Pediatrics, University of Alabama at Birmingham 35294, USA.
Vallet
B
B
Winn
M J
MJ
Caufield
J B
JB
King
C E
CE
Chapler
C K
CK
Cain
S M
SM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001784:Blood Gas Analysis; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003840:Deoxycholic Acid / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D006614:Hindlimb / Q000098:blood supply / Q000502:physiology; D007150:Immunohistochemistry; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D014662:Vasoconstrictor Agents; D003840:Deoxycholic Acid; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D009638:Norepinephrine