Adrenergic modulation of calcitonin gene-related peptide (CGRP)-containing nerve-mediated vasodilation in the rat mesenteric resistance vessel

Kawasaki, Hiromu; Nuki, Chikako; Saito, Akira; Takasaki, Koichiro

doi:10.1016/0006-8993(90)91263-g

Cited by 101 publications

(77 citation statements)

References 8 publications

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“…In contrast, NO and other endothelial-derived factors, are also involved as mediators of the responses to both NANC-induced stimulation and exogenous haCGRP in the same circuit. Finally, we suggest that, in accordance with previous reports in vascular models derived from larger animal species (Kawasaki et al, 1990;Rubino and Burnstock, 1996;Brain and Grant, 2004) NANC perivascular nerves act as a physiological antagonist of the autonomic nerve-dependent increase of perfusion pressure in the arterial mesenteric bed of the mouse.…”

Section: Discussionsupporting

confidence: 91%

“…For example, CGRP is known as the main neuropeptide involved in the capsaicin-sensitive nerve-induced vasodilatation of the rat mesenteric vascular bed (Kawasaki et al, 1988(Kawasaki et al, , 1990. Binding of capsaicin to specific neuronal receptors, prompts release of neurotransmitters such as CGRP from the peripheral ending of sensory nerves followed by a desensitization of the mechanism (Rubino and Burnstock, 1996).…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the non‐adrenergic/non‐cholinergic response to perivascular nerve stimulation in the double‐perfused mesenteric bed of the mouse

Legros

Tirapelli

Brochu

et al. 2007

British J Pharmacology

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Background and purpose: Calcitonin gene-related peptide (CGRP), a capsaicin-sensitive neuromodulator of splanchnic vascular tone in several animal species, remains poorly investigated in mouse models. We therefore assessed whether endogenous CGRP is a non-adrenergic/non-cholinergic (NANC) neuromodulator in the mesenteric vascular bed of the mouse. Experimental approach: Arterial and venous changes in perfusion pressure in response to perivascular nerve stimulation (PNS) were monitored in the mouse mesenteric bed under basal conditions or precontracted with KCl (artery) or U46619 (vein) in circuits pretreated with guanethidine, atropine, indomethacin and prazosin. Arterial responses to NANC were also characterized with a CGRP1 antagonist, haCGRP 8À37. Finally, the PNS-induced release of arterial CGRP was measured by enzyme immunoassay. Key results: HaCGRP 8À37 enhanced PNS-induced arterial increases in perfusion pressure under basal tone. PNS-induced stimulation of NANC triggered an haCGRP 8À37 or capsaicin-sensitive reduction in perfusion pressure of the pre-contracted arterial bed only. Chemical removal of the endothelium inhibited PNS-and haCGRP-induced reduction in perfusion pressure in the arterial mesenteric bed. Responses to NANC nerves were reduced by guanylate and adenylate cyclase inhibitors (1H-[1,2,4]oxadiazole[4,3-a] quinoxalin-1-one (ODQ)) and [9-(tetrahydro-2-furanyl)-9H-purin-6-amine] (SQ 22 536), respectively. A neuronal NOS inhibitor (7-nitroindazole; 7-NI) also enhanced the response to NANC in vessels from wild-type, eNOS KO but not iNOS KO mice. Finally, PNS enhanced the release of immunoreactive CGRP from the perfused arterial mesenteric bed. Conclusions and implications: Our study demonstrates a role for CGRP in the NANC-dependent reduction in perfusion pressure of the arterial but not venous mesenteric bed of the mouse. (2007) Keywords: CGRP; haCGRP 8À37 ; neuronal nitric oxide synthase; arterial mesenteric vasculature; mouse model British Journal of Pharmacology

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Characterization of the non‐adrenergic/non‐cholinergic response to perivascular nerve stimulation in the double‐perfused mesenteric bed of the mouse

Legros

Tirapelli

Brochu

et al. 2007

British J Pharmacology

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“…The PNS-induced vasoconstrictor response in the rat mesenteric arteries has been shown to be mediated by activation of sympathetic adrenergic nerves, since a neurotoxin (tetrodotoxin), an adrenergic neuron blocker (guanethidine), an adrenergic neurotoxin (6-hydroxydopamine) and an a1-adrenoceptor antagonist (prazosin) abolished the response. [21][22][23] On the other hand, FDR showed an unchanged vasoconstrictor response to exogenously applied NE, which is mediated by the postsynaptic a1-adrenoceptor. Taken together, the present findings strongly suggest that neurotransmitter NE release from sympathetic nerve terminals is facilitated by enhanced sympathetic nerve activity in a hyperinsulinemic state without affecting sensitivity of postsynaptic a1-adrenoceptors.…”

Section: Discussionmentioning

confidence: 99%

Hyperinsulinemia induces hypertension associated with neurogenic vascular dysfunction resulting from abnormal perivascular innervations in rat mesenteric resistance arteries

et al. 2011

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We previously reported that chronic hyperinsulinemia and insulin resistance induced by fructose-drinking loading elicited hypertension associated with abnormal neuronal regulation of vascular tone in an in vivo study using pithed rats. Therefore, to further clarify the detailed mechanisms of perivascular nervous system malfunction induced by chronic hyperinsulinemia, we investigated the neurogenic vascular responses and distribution of perivascular nerves using mesenteric vascular beds isolated from fructose-loaded rats with hyperinsulinemia. Male Wistar rats (6 weeks old) received 15% fructose solution as drinking fluid for 10 weeks (fructose-drinking rats, FDR), which resulted in significant increases in plasma levels of insulin, the glucose-insulin index, blood norepinephrine (NE) levels and systolic blood pressure, but not blood glucose levels, when compared with normal water-drinking rats (control rats). In perfused mesenteric vascular beds of FDR, enhanced adrenergic nerve-mediated vasoconstriction with no effect on NE-induced vasoconstriction and decreased calcitonin gene-related peptide (CGRP)-containing nerve-mediated vasodilation with no effect on CGRP-induced vasodilation were observed. Immunohistochemistry studies showed increased density of neuropeptide Y immunopositive adrenergic fibers and reduced density of CGRP immunopositive fibers in mesenteric arteries of FDR. Furthermore, FDR showed decreased CGRP content in dorsal root ganglia. These findings suggest that dysfunction of the neuronal vascular control system resulting from abnormal innervation of mesenteric perivascular nerves induced by the hyperinsulinemic state is responsible for the development of hypertension in FDR.

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“…The presence of excitatory CGRP receptors on sensory neurons, within the dorsal root ganglia, which may act as stimulatory autoreceptors, has been reported recently [45]. Inhibition of CGRP release by α2-adrenoceptors, located presynaptically on sensory neurons [46], and the ability of CGRP to inhibit the release of norepinephrine from sympathetic nerves [47] in the rat mesentery circulation, suggest that reciprocal interactions can occur between the noradrenergic constrictor system and the sensory (vasodilatatory) system, and are indicative of an important role for CGRP in the regulation of peripheral blood flow.…”

Section: Prejunctional Modulation Of Cgrp Releasementioning

confidence: 91%

CGRP and migraine: neurogenic inflammation revisited

Geppetti

Capone²,

Trevisani

et al. 2005

J Headache Pain

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The term 'neurogenic inflammation' refers to a series of proinflammatory responses produced by the stimulation of peripheral terminals of a subset of primary sensory neurons and the subsequent release of the neuropeptides, calcitonin gene-related peptide (CGRP) and the tachykinins, substance P (SP) and neurokinin A (NKA) [1]. The neurons that produce inflammation comprise a heterogeneous cell population with A-delta and C fibres, defined as polymodal nociceptors because they sense thermal, chemical and high-threshold mechanical stimuli. These neurons express on their plasma membrane a large panel of excitatory and inhibitory receptors and channels, and some of these signalling proteins have been successfully used as targets for analgesic or anti-inflammatory drugs. Among the channels expressed on peptidergic primary sensory neurons, transient receptor potential vanilloid-1 (TRPV1) [2], activated by the xenobiotic capsaicin, the pungent ingredient of plants of the genus Capsicum, is of paramount importance. Capsaicin produces burning pain by stimulating TRPV1 and by releasing sensory neuropeptides causes neurogenic inflammation. However, high concentrations/doses of capsaicin have the ability, after an initial excitatory phase, to desensitise the sensory nerve terminals, thus reducing the transmission of sensory/pain signals and abolishing neurogenic inflammation [3, 4]. This specific feature of capsaicin has greatly contributed to define the role of this subset of sensory nerves in pathophysiological models of human diseases and has been Pierangelo Geppetti Jay Guido Capone Marcello Trevisani Paola Nicoletti Giovanni Zagli Maria Rosalia Tola Abstract For more than a century neurogenic inflammation has been proposed to have a role in various human diseases. The present review will cover the conceptual steps of the itinerary that has led to the conclusion that neurogenic inflammation is important in migraine. Of particular relevance for the object of this article is the observation that tachykinindependent neurogenic inflammatory responses are evident in rodents, but much less pronounced or absent in other mammal species, including man, whereas neurogenic vasodilatation, most likely mediated by CGRP, occurs in most mammalian species and also in man. Recent evidence that a CGRP receptor antagonist was effective in the treatment of migraine attack supports the hypothesis that neurogenic vasodilatation is a major underlying mechanism of migraine.

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Adrenergic modulation of calcitonin gene-related peptide (CGRP)-containing nerve-mediated vasodilation in the rat mesenteric resistance vessel

Cited by 101 publications

References 8 publications

Characterization of the non‐adrenergic/non‐cholinergic response to perivascular nerve stimulation in the double‐perfused mesenteric bed of the mouse

Characterization of the non‐adrenergic/non‐cholinergic response to perivascular nerve stimulation in the double‐perfused mesenteric bed of the mouse

Hyperinsulinemia induces hypertension associated with neurogenic vascular dysfunction resulting from abnormal perivascular innervations in rat mesenteric resistance arteries

CGRP and migraine: neurogenic inflammation revisited

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