Role of adenosine in regulation of regional cerebral blood flow in sensory cortex

Abstract

We have previously demonstrated that rat pial arterioles located on the somatosensory cortex dilated in response to contralateral sciatic nerve stimulation (SNS). We hypothesized that the vasodilation was mediated by adenosine, released as a result of somatosensory cortex activation. To test this hypothesis, we examined the effects of SNS (0.15-0.2 V, 5 ms, 5 Hz for 20 s) on pial arterioles under conditions of altered adenosine availability. Cerebrospinal fluid (CSF) adenosine was altered by perfusing mock CSF, under a cranial window in anesthetized rats, containing either an adenosine uptake competitor (dipyridamole or inosine) or an adenosine receptor blocker (theophylline). With CSF only, SNS caused pial arterioles (resting diam, 29 +/- 1 micron) to dilate by 38 +/- 10% (peak magnitude) for 32 +/- 2 s. Dipyridamole (10(-6) M) significantly (P less than 0.02) enhanced both the magnitude (to 62 +/- 12%) and duration (to 68 +/- 10 s) of the response. Similarly, inosine (10(-3) M) significantly (P less than 0.02) potentiated the vasodilative response from resting values of 27 +/- 5% and 34.8 +/- 4.1 s to 37 +/- 6% and 89.6 +/- 14.1 s. In contrast, theophylline (5 x 10(-5) M) significantly (P less than 0.001) attenuated arteriolar vasodilation from resting values of 38 +/- 5% and 29.3 +/- 1.2 s to 18 +/- 3% and 22.0 +/- 0.9 s. Neither dipyridamole nor theophylline had a significant effect on neuronal response (sensory-evoked response) recorded from the somatosensory cortex. These results suggest that adenosine is involved in the regulation of pial vasodilation during cerebral cortical activation.

Lack of Sympathetic and Cholinergic Influences on Cerebral Vasodilation Caused by Sciatic Nerve Stimulation in the Rat

“…This experi mental paradigm allows examination of the cerebral microcirculation during cortical activation. In a pre vious study using this technique, we found that changes in adenosine availability altered the arteri olar response, supporting the hypothesis that ade nosine is involved in the regional metabolic regula tion ofCBF (Ko et al, 1990). On the other hand, the pial vessels are known to be innervated by fibers arising in extracerebral sympathetic and para sympathetic fibers (Busija and Heistad, 1984;Ed-nucleus basalis magnocellularis (the major source of in tracerebral acetylcholine neurons, n = 7).…”

Functional neuroimaging of normal human sleep by positron emission tomography

“…During this metabolic response, several compounds, which mediate the vasodilatory haemodynamic response in the surrounding microcirculation, are produced. The principal vectors of this vascular response are K + ions (Paulson and Newmann 1987;Kuchinsky 1997), H + ions (Kuchinsky 1997), nitric oxide (NO; Northington et al 1992;Dirnagl et al 1993) and adenosine (Ko et al 1990;Dirnagl et al 1993), although peptides (Edvinsson 1985), prostaglandins (PG; Leer et al 1993) and kinines (Itakura and Okuno 1993) have also been implicated in these processes. These events occur near the synapses and a number of arguments suggest that regional CBF primarily re¯ects local synaptic activity (Jueptner and Weiller 1995).…”

Changes in Pial Arteriolar Diameter and CSF Adenosine Concentrations during Hypoxia

“…Several studies have been published docu menting increases in adenosine concentration in brain, interstitial fluid, and CSF under conditions in which oxygen supply to the brain is decreased (Winn et al, 1981b;Van Wylen et al, 1986;Phillis et al , 1987). Moreover, adenosine receptor antag onists and uptake inhibitors have been utilized ex tensively in studies attempting to define the role of this nucleoside in blood flow regulation (Ko et al , 1990;Morii et al , 1987;Park and Gidda y, 1990;Phillis et al, 1989).…”