Nitric oxide from neuronal NOS plays critical role in cerebral capillary flow response to hypoxia.
We investigated, using a direct, intravital microscopic technique, whether nitric oxide (NO) from neuronal nitric oxide synthase (nNOS) plays a role in the cerebral capillary flow response to acute hypoxia. Erythrocyte flow in subsurface capillaries of the frontoparietal cortex of adult Sprague-Dawley rats was visualized using epifluorescence videomicroscopy after fluorescent labeling of red blood cells (RBC) in tracer concentrations. The velocity of labeled RBC in individual capillaries was measured off-line using an image analysis system. Hypoxia was produced by lowering the inspired O2 concentration to 15% for 5 min in control animals and in those pretreated with the selective nNOS inhibitor 7-nitroindazole (7-NI; 20 mg/kg ip). In the control group, hypoxia increased RBC velocity by 34 +/- 8%. In the group treated with 7-NI, this response was reversed to a statistically significant 8 +/- 3% decrease. This paradoxical response to hypoxia after 7-NI was observed in nearly all capillaries. 7-NI itself decreased the baseline RBC velocity by 12 +/- 4%. The cerebral hyperemic response to hypoxia was also assessed with the laser Doppler flow (LDF) technique. In control animals, hypoxia produced a 33 +/- 6% increase in LDF, similar to the increase in RBC velocity. After 7-NI treatment, the response to hypoxia was moderately attenuated but still significant at a 19 +/- 2% increase in LDF. These results support the role of NO from nNOS in the cerebral hyperemic response to hypoxia. They imply that 7-NI interfered with a physiological mechanism that was fundamental to cerebral capillary flow regulation and provide direct evidence that cerebral capillary perfusion may be dissociated from a concurrent change in regional tissue perfusion as reflected by LDF. In conclusion, NO from nNOS contributes to the maintenance of RBC flow in cerebral capillaries and plays a critically important role in the selective regulation of cerebral capillary flow during hypoxia.
Hudetz
A G
AG
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Shen
H
H
Kampine
J P
JP
D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D002196:Capillaries / Q000502:physiology; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000503:physiopathology*; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D014741:Video Recording
D004791:Enzyme Inhibitors; D006454:Hemoglobins; D007191:Indazoles; D002245:Carbon Dioxide; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010100:Oxygen; C080122:7-nitroindazole