This study describes a closed cranial window technique that allows the observation and measurement of rat pial arterioles and venules in situ. The resolving power of this system is 1–2 μm. Using this sensitive technique, we characterized the responses to 7% carbon dioxide inhalation and adenosine in arterioles (10–70 μm) and venules (15–100 μm). During carbon dioxide inhalation, larger arterioles (>40μm) dilated more than smaller arterioles (<20 μm). There was limited vasoreac-tivity of pial venules during CO2 inhalation. Dilation of arterioles was initially observed with an adenosine concentration of 10−8 M. Almost a twofold increase in diameter was noted at 10−3 M. In contrast to the effect of CO2 inhalation, the degree of dilation with topical application of adenosine was not size dependent. Pial venules did not respond to adenosine. The technique for observation of pial vessels using the closed cranial window and for measurement of vessel diameter by video camera system microscopy is a powerful tool for studying in vivo the cerebral circulation in the rat.

The present study documents the microvascular response of the pial circulation in sensory hindlimb cortex to sciatic nerve stimulation. Rats, anesthetized with alpha-chloralose and urethan, were equipped with closed cranial windows, and pial arteriolar diameter was measured during stimulation of the contralateral sciatic nerve. The effects of varying stimulus frequency, intensity, and duration were examined. Optimal stimulus frequency was 5 Hz, but response diminished significantly beyond 10 Hz. Optimal stimulus intensity was 0.2 V. At higher stimulus strength, arteriolar dilation was reduced, but systemic blood pressure rose significantly. At low stimulus frequency and intensities, pial arterioles responded to stimulation with a consistent pattern: initial delay of 1.4 s followed by abrupt dilation to a peak magnitude, subsequent decline to a lesser but still dilated state, and recovery to a resting diameter after the cessation of stimulation. No consistent response profile was discernible at high stimulus intensity and/or frequency. This vasodilatory response was discretely restricted to a limited number of arterioles, confined to the hindlimb somatosensory cortex as confirmed by sensory evoked response. The response of the pial circulation provides a well-characterized model for analysis of brain microcirculation, which presumably is linked to cerebral metabolism.

We studied the effects of the methylxanthine theophylline, an adenosine receptor blocker, on cerebral circulation. Cerebral blood flow (CBF) was measured by the retroglenoid outflow and microsphere techniques, and pial circulation changes were observed through a closed cranial window. Intraperitoneal administration of theophylline in normoxic animals resulted in a biphasic response of pial vessels and CBF. At low concentrations (0.05 mumol/g) of theophylline, pial vessel diameter and CBF decreased, whereas vasodilatation and hyperemia were observed at higher levels. After intraperitoneal administration of either 0.05 or 0.2 mumol/g, hypoxic hyperemia was attenuated both during short (c. 30 s) and sustained (c. 2-3 min) hypoxia, as was hypoxic pial arteriolar vasodilatation. These actions of theophylline appear to be due to adenosine receptor blockade, since micromolar concentrations were achieved in cerebrospinal fluid (CSF), and no increases in adenosine 3',5'-cyclic monophosphate concentrations in brain were noted. Moreover, theophylline (either intraperitoneal or topical) blocked pial vasodilatation caused by topically applied adenosine, but had little effect on hypercarbic hyperemia or pial vasodilatation induced by topically applied acetylcholine. The results of these studies suggest that adenosine is involved in the maintenance of resting cerebral vascular tone and has a paramount role in the regulation of CBF during hypoxia.

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