Nicotine stimulation of the medulla increases blood flow of the common carotid artery in cats

Microinjection of nicotine or glutamate into the dorsal facial area (DFA) of the medulla increases blood flow of common carotid artery (CCA). Whether there is a causal relationship between these two events is not known. Various agonists and antagonists for the nicotinic and glutamatergic receptors were microinjected through a four-barrel tubing into the DFA of anesthetized cats. Microinjections of nicotine [a non-selective nicotinic acetylcholine receptor (nAChR) agonist], choline (a selective alpha 7-nAChR agonist), glutamate or KCl induced a modest increase in CCA blood flow. The nicotine- and choline-induced increases were reduced by alpha-bungarotoxin (an alpha 7-nAChR antagonist) as well as MK-801 (a non-competitive NMDA receptor antagonist) or glutamate diethylester (a competitive AMPA/kainate receptor antagonist). The glutamate or KCl-induced increases were blocked by MK-801 and glutamate diethylester, but not by alpha-bungarotoxin. In conclusion, activation of nAChRs primarily via alpha 7-nAChR caused a release of glutamate, which in turn activated NMDA and AMPA receptors, while cholinergic substance was not released into the DFA to activate the nicotinic receptor. Crown Copyright (C) 2009 Published by Elsevier B.V. All rights reserved

Nitric oxide and glutamate in the dorsal facial area regulate common carotid blood flow in the cat

Nitric oxide (NO) or glutamate stimulation of dorsal facial area (DFA) increases blood flow in the common carotid artery (CCA), which supplies intra-and extra-cranial tissues. Nitrergic fibers and neurons as well as preganglionic cholinergic neurons are present in the DFA. We hypothesized the presence of nitrergic-glutamatergic fibers and preganglionic nitrergic-Cholinergic neurons in the DFA that are involved in the regulation of CCA blood flow. In microdialysis studies, perfusion of the DFA with S-nitroso-Nacetylpenicillamine (SNAP, an NO donor) increased the glutamate concentration in the dialysate. This effect was abolished by co-perfusion of methylene blue (a guanylyl cyclase inhibitor). Intra-DFA injection of L-arginine (an NO precursor) or glutamate increased CCA blood flow. The L-arginine-induced flow increase was reduced by prior administration of NG-nitro-arginine methyl ester (L-NAME, a non-specific NO synthase inhibitor), 7-nitroindazole (7-NI, a relatively selective neuronal NO synthase inhibitor), D-2amino-5-phosphonopentanoate (D-AP5, a competitive NMDA receptor antagonist), or glutamate diethylester (GDEE, a competitive AMPA receptor antagonist). The glutamate-induced blood flow increase was reduced by prior administration of L-NAME, 7-NI, or methylene blue. The induced increase in CCA blood flow, however, was not affected by endothelial NO synthase inhibitor. The findings indicate that NO-signal transduction within the DFA might cause glutamate release from presynaptic nitrergic-glutamatergic fibres and that the released glutamate activates NMDA/AMPA receptors on preganglionic nitrergic-cholinergic neurons in the nucleus to activate neuronal NO synthase and guanylyl cyclase in the neurons, leading to an increase in CCA blood flow. These findings may be important for developing therapeutic strategies for the diseases associated with CCA blood flow. (C) 2008 Elsevier B.V. All rights reserved

Nicotine activation of neuronal nitric oxide synthase and guanylyl cyclase in the medulla increases blood flow of the common carotid artery in cats

Individual activation of nicotinic acetylcholine receptor (nAChR) or nitric oxide (NO) synthase in the dorsal facial area (DFA) increases blood flow of common carotid artery (CCA) supplying intra- and extra-cranial tissues We investigated whether the activation of nAChR initiated the activation of NO synthase and guanylyl cyclase to increase CCA blood flow in anesthetized cats Microinjections of nicotine (a nonselective nAChR agonist) or choline (a selective alpha 7-nAChR agonist) in the DFA produced increases in CCA blood flow ipsilaterally These Increases were significantly reduced by pretreatment with NG-nitroarginine methyl ester (L-NAME a non-specific NO synthase inhibitor) 7-nitroindazole (7-NI a relatively selective neuronal NO synthase inhibitor) or methylene blue (MB a guanylyl cyclase inhibitor) but not by that with N5-(1-iminoethyl)-L-ornithine (t-NIO a potent endothelial NO synthase inhibitor) Control microinjection with D-NAME (an Isomer of L-NAME) artificial cerebrospinal fluid or DMSO (a solvent for 7-NI) did not affect resting CCA blood flow nor did they affect nicotine- or choline-induced response In conclusion activation of nAChR at least alpha 7-nAChR led to the activation of neuronal NO synthase and guanylyl cyclase in the DFA which Induced an increase in CCA blood flow (C) 2010 Published by Elsevier Ireland Lt

GLUTAMATE RELEASE UPON PURINERGIC ACTION IN THE DORSAL FACIAL AREA OF THE MEDULLA INCREASES BLOOD FLOW IN THE COMMON CAROTID ARTERY IN CATS

Interactions of glutamatergic and purinergic actions in the medulla regulate important cardiovascular functions. The glutamatergic action in dorsal facial area (DFA) of the medulla increases blood flow of common carotid artery (CCA) in cats. We hypothesized that interactions of glutamatergic and purinergic actions in the DFA may regulate the CCA blood flow. Purinergic and glutamatergic agonists and antagonists were microinjected into the DFA through a four-barrel tubing in anesthetized cats. Drug effects were evaluated by changes in the CCA blood flow. Microinjection with 20 nmol ATP or alpha,beta-methylene-ATP (alpha,beta-MeATP, a P2 purinergic receptor agonist) induced an increase of the CCA blood flow. This increase was dose-dependently reduced by prior administration with 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX, a specific PI purinergic receptor antagonist), or pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, a selective P2 purinergic receptor antagonist) as well as with MK-801 (a non-competitive NMDA receptor antagonist) or glutamate diethyl ester (GDEE, a competitive AMPA/kainate receptor antagonist). It was almost completely blocked by administrations with combined maximal doses of P1 and P2 receptor antagonists as well as NMDA and AMPA receptor antagonists. Nevertheless, P1 receptor agonist induced only mild and poorly reproducible increase in the CCA blood flow. In conclusion, prominent P2 and minor P1 purinergic receptors appear to be present in the DFA; the purinergic activation can mediate a release of glutamate that stimulates NMDA and AMPA to induce the increase of the CCA blood flows. These findings may provide important information for developing therapeutic strategy for diseases involving the CCA blood flow, such as hypertensive disease and cerebral ischemia. Crown Copyright (c) 2009 Published by Elsevier Ltd on behalf of IBRO. All rights reserved