Cerebral blood flow was measured with the 14C-ethanol technique in 8 regions (frontal, parieto-temporal and occipital cortex, caudate nucleus, thalamus, cerebellum, mesencephalon, and pons) of rats. The highest flow values (83-89.5 ml/100 g/min) were found in cortical areas, whereas pons had the lowest flow (48 ml/100 g/min). Intravenous infusion of noradrenaline or adrenaline markedly reduced rCBF (by 22-48% of control levels) in all regions except thalamus, mesencephalon, and pons. The noradrenaline-induced reduction was blocked, and the effect of adrenaline reversed, after pretreatment with the alpha-receptor antagonist, phentolamine. Isoprenaline infusion markedly augmented rCBF in thalamus, mesencephalon, pons, and also in the caudate nucleus. The response was reduced by the beta-receptor antagonist, propranolol. The experiments show the presence and heterogenous distribution in the cerebrovascular bed of slpha- and beta-adrenoceptors that can be activated by sympathomimetics given systematically. If noradrenaline was allowed to pass the blood-brain barrier after osmotic opening with urea, an increased regional flow was obtained, probably due to a mechanism where the vasodilator effect secondary to activation of cerebral metabolism predominated over the direct vasoconstrictor effect of the amine.

Rabbit leptomeningeal arteries contain granular cells resembling mast cells that frequently contact autonomic and sensory nerve profiles. In the present in vitro study, we determined whether these cells could be stimulated by substance P (SP) and calcitonin gene-related peptide (CGRP), which are stored and released by sensory C fibers. Immunohistochemistry of the middle cerebral artery showed that 5-HT was stored only in mast cell-like granules. This pool of 5-HT decreased in a dose-dependent manner when exogenous SP and CGRP were added to the incubation solution or when endogenous neuropeptides were released from nerve terminals by capsaicin. The simultaneous administration of CGRP and SP induced a dramatic exocytosis and a 5-HT release significantly greater than the sum of the individual effects of the two neuropeptides. We conclude that, as in classical connective tissue mast cells, the amine content of these granular cells can be released by a degranulation process induced by neuropeptides. The effects of capsaicin suggest that this phenomenon can be triggered by axon reflex of C fibers. The data also provide the first evidence of a synergistic action of SP and CGRP on mast cell degranulation.

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