Role of endothelial nitric oxide in microvascular oxygen delivery and consumption.
Nitric oxide (NO) is an important signaling molecule modulating diverse processes such as vasodilation, neurotransmission, long-term potentiation, and immune responses. The endothelium contributes a significant fraction of NO from endothelial NO synthase (eNOS). The objective of this work was to analyze the role of eNOS in the modulation of oxygen supply to the tissues and in adaptation to maintain oxygenation uncompromised. Oxygen delivery and consumption were measured in the microcirculation of homozygous mutant endothelial nitric oxide synthase-deficient (eNOS(-/-)) and wild-type mice. Animals were implanted with a dorsal window chamber, allowing us to assess the intact microvascular system. Hemodynamics and oxygen tension were assessed in the microcirculation of conscious animals. The eNOS(-/-) mice had significantly higher blood pressure and lower heart rate (146 +/- 8 mm Hg, 401 +/- 17 bpm) than wild type (127 +/- 6 mm Hg, 428 +/- 20 bpm). Microvascular hemodynamic parameters were not significantly different between groups. The eNOS(-/-) animals delivered less oxygen to the microcirculation and released more oxygen to the tissue; both differences were statistically significant compared to wild type. The arteriolar vessel wall oxygen gradient, a measure of vascular smooth muscle cells and endothelial cell wall oxygen consumption, was significantly lower for eNOS(-/-) than for wild type, suggesting that the inhibition of eNOS is an antianoxia (oxygen sparing) mechanism. Finally, the findings of the study support the argument that NO availability limits oxygen consumption by the tissue.
Cabrales
Pedro
P
La Jolla Bioengineering Institute, La Jolla, CA 92037, USA. pcabrales@uscd.edu
Tsai
Amy G
AG
Frangos
John A
JA
Intaglietta
Marcos
M
D000818:Animals; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D001808:Blood Vessels / Q000166:cytology / Q000502:physiology; D002196:Capillaries / Q000502:physiology; D042783:Endothelial Cells / Q000201:enzymology; D006339:Heart Rate / Q000235:genetics / Q000502:physiology; D006454:Hemoglobins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008833:Microcirculation / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology*
D006454:Hemoglobins; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D010100:Oxygen