COUPLING OF CEREBRAL BLOOD-FLOW TO NEURONAL ACTIVATION - ROLE OF ADENOSINE AND NITRIC-OXIDE

We studied the role and relationship of the putative mediators of coup ling of cerebral blood flow (CBF) and neuronal activation, adenosine ( Ado) and nitric oxide (NO). Topical brain application over the whisker barrel cortex of anesthetized rats (n = 24) of the Ado receptor antag onist theophylline (Theo, 5 x 10(-5) M) for 30 min reduced the CBF res ponse to deflection of the contralateral whiskers from 17.9 +/- 3.0% o f baseline to 10.6 +/- 2.7% (P < 0.05). Coapplication of Thee (5 x 10( -5) M) and the NO synthase blocker N-omega-nitro-L-arginine (L-NNA, 10 (-3) M) for 30 min led to a further reduction in the CBF response to w hisker stimulation to 7.5 +/- 1.3% (P < 0.05 compared with Theo alone) . The CBF effect of sodium nitroprusside (10(-5) M) was not affected b y Theo-L-NNA coapplication (122 +/- 25 vs. 140 +/- 25%, n = 5). Applic ation of adenosine deaminase (1 U/ml, n = 5) reduced the CBF response to whisker stimulation from 18.2 +/- 0.7 to 10.7 c 1.9% (P < 0.05). Su perfusion of L-NNA (10(-3) M, 30 min, n = 7) attenuated the CBF respon se to application of Ado (10(-4) M) from 39.4 +/- 10.4 to 22.9 +/- 10. 5% (P < 0.05). N-omega-nitro-D-arginine did not affect the CBF respons e to Ado (n = 5). We conclude that 1) Ado is involved in coupling of C BF to neuronal activation, 2) NO is involved in this response as well, and 3) there is an interaction between the vasodilator pathways of Ad o and NO.