The Effects of Dipyridamole and Theophylline on Rat Pial Vessels during Hypocarbia

Abstract

Hypocarbia results in an increase in brain adenosine concentrations, presumably because of brain hypoxia associated with hypocarbic vasoconstriction. It was hypothesized that adenosine limits the degree of hypocarbic vasoconstriction. To test this hypothesis, the effects of dipyridamole and theophylline on CO2 reactivity during hypocarbia were investigated in anesthetized rats. Dipyridamole should reduce the vasoconstriction by potentiating adenosine action, whereas theophylline should increase the vasoconstriction by blocking adenosine receptors. Cortical pial arterioles of mechanically ventilated and anesthetized rats were displayed on a video monitor system through a closed cranial window. Arterial blood pressure and oxygen tension were stable. CO2 reactivity, formulated as 100 x [Δ diameter (μm)/resting diameter (μm)]/Δ PaCO2 (mmHg), in the hypocarbic phase was calculated before and after topical superfusion of dipyridamole (10−6 M; n = 7) and theophylline (5 × 10−5 M; n = 6). CO2 reactivity was significantly decreased after superfusion of dipyridamole (0.57 ± 0.08; mean ± SEM) as compared with mock cerebrospinal fluid (CSF) (0.97 ± 0.17, p < 0.05, n = 7). On the other hand, CO2 reactivity after superfusion of theophylline was increased (1.63 ± 0.28) as compared with mock CSF (1.00 ± 0.20, p < 0.05, n = 6), indicating that adenosine is involved in hypocarbic vasoconstriction.