Local cholinergic mechanisms participate in the increase in cortical cerebral blood flow elicited by electrical stimulation of the fastigial nucleus in rat.
We sought to determine whether the increase in regional cerebral blood flow (rCBF) elicited within the cerebral cortex (CX) by electrical stimulation of the fastigial nucleus (FN) of the cerebellum is: prevented by local application of the muscarinic cholinergic receptor antagonist, atropine and temporally correlated with a stimulus-locked release of acetylcholine (ACh) from the cortical surface. Rats were anesthetized, paralyzed, ventilated, with arterial blood gases controlled and arterial pressure maintained within the autoregulated range. Bilateral craniotomies were performed over a standardized region of the sensory motor CX and superfusion devices stereotaxically positioned on the cortical surface. Cortical surface temperature, as well as pH, pCO2 and pO2 of the solutions applied to the cortex were also carefully controlled. rCBF was measured in dissected regions of frontal (FCX), parietal (PCX), and occipital cortices (OCX), caudate nucleus (CN), and hippocampus (HIPP) by the Kety principle using [14C]iodoantipyrine as indicator. Resting rCBF (ml/100 g/min) in unoperated control animals ranged from 70 +/- 5 in HIPP to 95 +/- 7 in PCX and was unaffected by bilateral craniotomies and placement of superfusion devices containing Kreb's bicarbonate buffer (vehicle) on the cortical surface. Local application of atropine (ATR, 100 microM) to the right PCX via the superfusion device did not affect resting rCBF. With FN stimulation rCBF increased bilaterally and symmetrically in all areas up to 227% in PCX. ATR application attenuated by 59% the FN-elicited increase in rCBF on the ipsilateral frontoparietal CX, without affecting blood flow in adjacent structures. ATR did not affect cortical cerebrovasodilation produced by hypercarbia (arterial pCO2 = 59.0 +/- 1.4 mm Hg). FN-stimulation resulted in a small (22%) but significant (P less than 0.05, n = 9) reduction in the release of [3H]ACh from the cortical surface, while supramaximal depolarization with 55 mM K+ increased [3H]ACh release by 251%. These studies indicate that: increases in cortical rCBF elicited by FN stimulation, but not hypercarbia, are in large part mediated by local muscarinic cholinergic receptors; resting rCBF is not tonically affected by muscarinic receptor activation; and the release of ACh from the cortical surface is, in general, reduced during FN-stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
D000109:Acetylcholine / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002531:Cerebellum / Q000502:physiology*; D002540:Cerebral Cortex / Q000098:blood supply* / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002799:Cholinergic Fibers / Q000378:metabolism / Q000502:physiology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001285:Atropine; D000109:Acetylcholine