7-nitroindazole abolishes cerebral capillary flow response to hypoxia

A. G. Hudetz, B. Biswal, J. P. Kampine

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Hypoxie cerebral vasodilatation is well known, however, the associated changes in capillary perfusion are unclear. A controversial question is whether endotheiium derived or neuronal nitric oxide (NO) may play a role in the hypoxic response. Our study had two objectives: (I) to determine by direct intravital microscopy the effect of moderate hypoxia on cerebral capillary flow velocity, and (2) to determine if the hypoxic response was altered after inhibition of neuronal NO synthase (nNOS). Cortical capillary circulation was studied using epifluorescence video-microscopy through a closed cranial window in pentobarbital anesthetized, artificially ventilated (30% 02, balance N2), adult Sprague-Dawley rats. FITC-labeled red blood cells (FRBC) were infused iv. to aid the measurement of capillary flow velocity off-line from 1 minute long video recordings using frame-by-frame analysis. Hypoxia was achieved by lowering the inspired O2 concentration to 15% for 2-6 minutes; arterial pressure was supported with methoxamine. A separate group of rats was treated with the selective nNOS inhibitor 7-nitroindazofe (7-NI, 20 mg/kg ip.) and the response to hypoxia was tested 45 minutes later. Resting FRBC velocity in 8 rats, 32 capillaries was 0.69 ±0.06 mm/s. In the untreated group (N=4), FRBC velocity increased during hypoxia from 0.62 ±0.08 to 0.86 ±0.13 mm/s (+38%, p<0.0001). After 7-NI treatment (N=4) FRBC velocity decreased from 0.76±0.09 to 0.66±0.08 mm/s (-13%, p<0.0005) and hypoxia further decreased FRBC velocity to 0.60±0.07 mm/s (-6%, p<0.05). These results suggest that (1) hypoxic hyperemia is associated with an increase in flow velocity in cortical capillaries, and (2) neuronal NOS activity is essential for the hypoxic capillary flow response. We speculate that in the absence of neuronal NO, physiological regulation of capillary flow may be disturbed, and a paradox response to hypoxia may occur due to shunting of red cells away from nutritive capillaries. Supported by AHA grant 95009340.

Original languageEnglish (US)
Pages (from-to)A542
JournalFASEB Journal
Issue number3
StatePublished - 1996
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Molecular Biology
  • Biochemistry
  • Biotechnology


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