A Pharmacologic Study on CO2 Responsiveness of Intracranial Pressure in Rats With Chronic Hypercapnia*

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Abstract

Study objectives

To investigate intracranial pressure (ICP) changes and their mechanisms in chronic hypercapnia.

Design

After 12 male Wistar rats were maintained in CO2-mixed air (mean PaCO2, 71.0 mm Hg) for 21 weeks, their ICP levels were measured during the breathing of 0, 5, 10, 12, and 14% CO2-mixed air before and after the IV administration of nitro-L-arginine methyl ester (L-NAME). The ICP responses to IV norepinephrine and IV adenosine were also tested. Ten rats that were maintained in room air served as the control group.

Results

The mean ICP in the study group (5.9 mm Hg) was not significantly different from the mean ICP in the control group. In the study group, the ICP response to changes in PaCO2 was significantly blunted when compared to the response seen in the control group. In both groups, IV norepinephrine significantly increased the ICP. In the control group but not in the study group, IV L-NAME suppressed the ICP response to changes in PaCO2. In both groups, IV adenosine significantly increased the ICP.

Conclusions

The ICP response to PaCO2 was blunted in rats with chronic hypercapnia, and the mechanism of this reduced response may involve nitric oxide.

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