Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence from our previous work suggests that neurogenic mediators contribute to the inflammation following ultraviolet (UV) irradiation of the skin. We have investigated whether calcitonin gene-related peptide (CGRP), substance P and nitric oxide (NO) participate in the cutaneous inflammatory reaction of the rat hind paw and ear to UV irradiation. Skin blood flow was measured by laser Doppler technique. Oedema was quantified using a spring loaded micrometer to measure ear thickness. UV irradiation of the rat skin lead to a long lasting increase in skin blood flow. This increase was dose dependently attenuated by the CGRP receptor antagonist CGRP-(8-37) (0.15 nmol in 25 microliters to 6.0 nmol in 25 microliters, s.c.) up to 51% with a maximum of effectiveness at 24 h post irradiation. The inhibitor of NO synthase NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, 25 nmol in 25 microliters, s.c.) attenuated skin blood flow by 38%. Concurrent injections s.c. of CGRP-(8-37) (1.5 nmol in 12.5 microliters) and L-NAME (25 nmol in 12.5 microliters) demonstrated an augmentive effect in attenuating skin blood flow. The tachykinin NK1 receptor antagonist CP-96,345 (6.0 nmol in 25 microliters, s.c.) attenuated skin blood flow by 27%. NG-Nitro-D-arginine methyl ester hydrochloride (D-NAME) and CP-96.344 showed no effects on skin blood flow after UV irradiation. CGRP-(8-37) (0.6 nmol in 10 microliters) i.d. and L-NAME (10 nmol in 10 microliters) i.d. had no effect of oedema formation after UV irradiation. Furthermore, post UV irradiation enhanced CGRP- and NO synthase-immunoreactivity in nerve fibres in the exposed skin area were visible. Taken these findings together we suggest the involvement of the neuropeptides CGRP and substance P and of neuronal NO on the vasodilatory component of the UV-induced inflammatory reaction of the rat skin. CGRP contributing to UV-induced vasodilation acts in an endothelial NO-independent manner.
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PMID:Calcitonin gene-related peptide, substance P and nitric oxide are involved in cutaneous inflammation following ultraviolet irradiation. 754 83

The existence of calcitonin gene-related peptide (CGRP) nerve fibers and CGRP receptors in the kidney and the coupling of the receptors to adenylyl cyclase suggest that CGRP participates in renal regulation. This study investigates the dose-effect relationship of CGRP on renal blood flow (RBF) and arterial conductance, glomerular filtration rate (GFR) and tubular excretion in Inactin-anesthetized, Sprague-Dawley rats. The contributions of endothelium-derived relaxing factor/nitric oxide in the renal actions of CGRP also were investigated via renal arterial injection of the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 0.5 or 5 mg/kg). Renal arterial infusion of CGRP (0.3-300 pmol/kg/min) did not affect mean arterial pressure or heart rate. Low doses of CGRP increased RBF, arterial conductance and GFR, but the highest dose reduced RBF and conductance without affecting GFR. High doses of CGRP also increased urine flow and excretions of Na+ and K+. The renal vasodilator but not the constrictor effect of CGRP was inhibited by both doses of L-NAME. The increase in GFR by the lowest dose of CGRP was attenuated by the low dose and abolished by the high dose of L-NAME. L-NAME did not inhibit the diuretic, natriuretic and kaliuretic effects elicited by high doses of CGRP. The results show that a low dose of CGRP causes renal vasodilatation via the release of endothelium-derived relaxing factor/nitric acid.
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PMID:Renal vascular and tubular actions of calcitonin gene-related peptide: effect of NG-nitro-L-arginine methyl ester. 771 12

1. Male, Long Evans rats were chronically instrumented with pulsed Doppler flow probes and intravascular catheters to permit assessment of the regional haemodynamic responses to human and rat adrenomedullin, to compare the responses to human adrenomedullin to those of human alpha-CGRP in the absence and presence of the CGRP1-receptor antagonist, human alpha-CGRP [8-37], and to determine the involvement of nitric oxide (NO)-mediated mechanisms in the responses to human adrenomedullin, relative to human alpha-CGRP. 2. Human and rat adrenomedullin (0.3, 1, and 3 nmol kg-1, i.v.) caused dose-dependent hypotension and tachycardia, accompanied by increases in renal, mesenteric and hindquarters flows and vascular conductances. At the lowest dose only, the hypotensive and mesenteric vasodilator effects of rat adrenomedullin were significantly greater than those of human adrenomedullin. 3. Human alpha-CGRP at a dose of 1 nmol kg-1 caused hypotension, tachycardia and increases in hindquarters flow and vascular conductance, but reduction in renal and mesenteric flows, and only transient vasodilatations in these vascular beds. These effects were substantially inhibited by human alpha-CGRP [8-37] (100 nmol kg-1 min-1), but those of human adrenomedullin (1 nmol kg-1) were not; indeed, the mesenteric haemodynamic effects of the latter peptide were enhanced by the CGRP1-receptor antagonist. 4. In the presence of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 183 nmol kg-1 min-1), there was only a slight, but significant, inhibition of the hindquarters hyperaemic vasodilator effect of human adrenomedullin, but not that of human alpha-CGRP. 5. These results indicate that the marked regional vasodilator effects of human (and rat) adrenomedullin are largely independent of NO and, in vivo, do not involve CGRP1-receptors.
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PMID:Regional haemodynamic effects of human and rat adrenomedullin in conscious rats. 773 84

Stimulation of capsaicin-sensitive sensory nerves induces gastric mucosal hyperemia, which is mediated in part by both calcitonin gene-related peptide (CGRP) and nitric oxide (NO). In the present study, we used in vivo microscopy in anesthetized rats to determine 1) whether these agents were released locally at the submucosal level and, if so, 2) whether CGRP dilates arterioles via release of endothelium-derived NO. Intragastric capsaicin (160 microM) dilated submucosal arterioles from 25 +/- 3 to 67 +/- 8 microns. The intragastric capsaicin-induced vasodilation was markedly reversed not only by intravenous administration of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) but also by submucosal suffusion of either L-NAME or the CGRP receptor antagonist human CGRP-(8-37). The latter findings indicate that both NO and CGRP are released locally at the submucosal level. Submucosal application of CGRP induced dose-dependent dilation of gastric submucosal arterioles, which was significantly attenuated by L-NAME. However, at the same degree of vasodilation (42 microns), the dilation induced with submucosal CGRP was much less attenuated by NO synthesis inhibition (-28%) compared with that induced with intragastric capsaicin (-79%). This indicates that endothelium-derived NO released by CGRP was not the only source of submucosal NO in the latter response. There must be another as yet undetermined source of submucosal NO, e.g., possibly nitroxidergic nerves.
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PMID:Interaction of endogenous nitric oxide and CGRP in sensory neuron-induced gastric vasodilation. 776 63

It has been suggested that capsaicin-induced hyperemia and mucosal protection occurs via calcitonin-gene-related peptide (CGRP) release from gastric afferent sensory neurons and nitric oxide (NO)-mediated vasodilation. The purpose of this study was to determine whether capsaicin and/or bile acid induced hyperemia is mediated by CGRP and/or NO. Male Sprague-Dawley rats (280-350 g) were anesthetized, and the glandular stomach (blood supply intact) was chambered between two plastic rings. Animals were divided into six groups. Normal saline (groups 1 and 4), the NO inhibitor N-nitro-L-arginine methyl ester (L-NAME; 3.75 mg/ml, groups 2 and 5), or the CGRP antagonist hCGRP8-37 (0.047 mg/ml, groups 3 and 6) was continuously infused intraarterially (ia) close to the stomach at a rate of 0.034 ml/min for 1 hr via a catheter inserted retrogradely into the splenic artery. Fifteen minutes after the onset of this infusion, the gastric mucosa was topically exposed to neutral saline solution for 15 min, followed by 160 microM capsaicin for 15 min. The mucosa was then injured by a 15-min exposure to either 5 mM acidified taurocholate (ATC, pH 1.2) in groups 1-3 or 10 mM ATC in groups 4-6. Gastric mucosal blood flow (ml/min/100 g) was continuously measured (laser doppler), and injury was assessed by measuring net transmucosal H+ flux, luminal accumulation of DNA, and histologic grading (0 = no injury to 3 = severe) by an independent observer. Intraarterial infusion of L-NAME significantly blocked the hyperemic response of topical capsaicin while having minimal effect on bile acid-induced hyperemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of calcitonin gene-related peptide and nitric oxide in gastric mucosal hyperemia and protection. 788 33

Responses to synthetic human adrenomedullin (ADM), a novel hypotensive peptide recently discovered in human pheochromocytoma cells, and calcitonin gene-related peptide (CGRP), a structurally related peptide, were investigated in the hindquarters vascular bed of the rat. Under conditions of controlled hindquarters blood flow, intraarterial injections of ADM (0.01-0.3 nmol) and of CGRP (0.03-0.3 nmol) caused dose-related decreases in hindquarters perfusion pressure and decreases in systemic arterial pressure. Following administration of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), hindquarters vasodilator and systemic depressor responses to ADM were significantly decreased, whereas L-NAME did not significantly decrease the vasodilator response to CGRP in either the hindquarters or systemic vascular beds. Following administration of the cyclooxygenase inhibitor, meclofenamate, vasodilator responses to ADM and to CGRP were not significantly decreased. When the relative vasodilator activity of the two peptides was compared on a nmol basis, responses to ADM were similar to responses with CGRP in the hindquarters vascular bed, whereas ADM was 30-100 fold less potent than CGRP in decreasing systemic arterial pressure. The present data demonstrate that ADM has significant vasodilator activity in the hindquarters vascular bed of the rat, that hindquarters vasodilator and systemic vasodepressor responses to ADM, but not to CGRP, are dependent upon the release of nitric oxide from the endothelium.
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PMID:L-NAME modulates responses to adrenomedullin in the hindquarters vascular bed of the rat. 796 46

The modulatory actions of nitric oxide on sensory nerves were investigated on dilator responses of the perfused rat mesentery to transmural nerve stimulation. N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis, caused a significant augmentation of vasodilator responses to transmural nerve stimulation, an effect which was abolished by L-arginine. L-NAME had no effect on vasodilator responses to exogenous calcitonin gene-related peptide. In preparations without endothelium L-NAME still caused potentiation of vasodilator responses to transmural nerve stimulation. Methylene blue, an inhibitor of guanylate cyclase, also significantly enhanced vasodilator responses to transmural nerve stimulation. After pretreatment with diethyldithiocarbamate to inhibit superoxide dismutase, vasodilator responses to transmural nerve stimulation were also potentiated. This response was abolished by exogenous superoxide dismutase. These findings suggest that endogenous nitric oxide modulates, in an inhibitory fashion, the actions of sensory nerves in the rat mesentery. The results also suggest that endogenous superoxide dismutase may participate in the regulation of the actions of sensory nerves via control of cellular superoxide anion level.
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PMID:Nitric oxide modulates responses to sensory nerve activation of the perfused rat mesentery. 822 87

The neuropeptide calcitonin gene-related peptide (CGRP) is a potent vasodilator in the microcirculation of many tissues including the skin and joint. In order to elucidate the mechanism of endogenous CGRP release, we have used a multiple site 133Xe clearance technique to measure local blood flow changes in response to agents injected intradermally in the rabbit. Capsaicin (100 nmol/site) and human alpha CGRP (3 pmol/site) stimulated similar increases in blood flow and, in both cases, the effect was totally abolished by the CGRP antagonist, CGRP8-37 (1 nmol/site). By contrast, the nitric oxide synthase inhibitor L-nitro arginine methyl ester (L-NAME, 30 nmol/site) had little effect on human alpha CGRP-induced vasodilation, but caused significant inhibition of the response to capsaicin (p < 0.05). These results show that increased blood flow in rabbit skin caused by exogenous CGRP is independent of nitric oxide. In addition, however, they suggest that nitric oxide is required for either the release of endogenous CGRP from capsaicin-sensitive nerves or its subsequent activity.
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PMID:The contribution of calcitonin gene-related peptide (CGRP) to neurogenic vasodilator responses. 831 13

The mechanism involved in the effects induced by the activation of perineural non-adrenergic non-cholinergic (NANC) nerves or by exogenous calcitonin gene-related peptide (CGRP) was investigated in the rat mesenteric vascular bed (MVB) perfused with Kreb's solution containing methoxamine and guanethidine. The activation of NANC terminals of the tissue was carried out by means of electrical field stimulation (EFS). An increase in the perfusion pressure of the preparations was observed in the presence of two inhibitors of nitric oxide synthase: NG-monomethyl-L-arginine (L-NMMA) (100 microM) and NG-nitro-L-arginine methyl ester (L-NAME) (100 microM). However L-NMMA and L-NAME did not modify the relaxant effect induced by EFS and exogenous CGRP. Furthermore the relaxant effect induced by EFS and exogenous CGRP was not affected by the removal of endothelium from the preparations. These results provide evidence that the vasodilation induced by NANC stimulation or by exogenous CGRP in MVB does not involve NO production.
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PMID:Nitric oxide is not involved in the effects induced by non-adrenergic non-cholinergic stimulation and calcitonin gene-related peptide in the rat mesenteric vascular bed. 841 51

This study was designed to explore the effect of ginsenosides, saponins from Panax ginseng, on the vasodilator nerve actions in the rat perfused mesentery and the mechanism of this effect. In the rat perfusion mesentery, when adrenergic nerves were blocked by guanethidine (5 x 10(-6) M) and vascular muscle tone was increased with methoxamine (5 x 10(-6)-10(-5) M), transmural field stimulation produced a frequency-dependent vasodilator response, which is due to the release of calcitonin gene-related peptide; ginsenosides significantly suppressed this vasodilator response in a concentration-dependent manner (3-30 micrograms mL-1). After pretreatment with saponin (50 micrograms mL-1, 3 min) to damage endothelial cells, this suppressing effect of ginsenosides was unaltered. However, the effect was abolished by N omega-nitro-L-arginine methyl ester (L-NAME) (10(-4) M), an inhibitor of nitric oxide synthesis and addition of L-arginine (3 x 10(-4) M) restored this suppressing effect. Methylene blue (10(-5) M), an inhibitor of guanylate cyclase, also abolished the suppressing effect of ginsenosides. However, ginsenosides did not alter the relaxation responses caused by exogenous calcitonin gene-related peptide administration. We conclude that ginsenosides can produce an inhibitory effect on the vasodilator response prejunctionally in the rat perfused mesentery and that this effect of ginsenosides may be mediated by nitric oxide released from non-adrenergic, non-cholinergic nerves.
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PMID:Effects of ginsenosides on vasodilator nerve actions in the rat perfused mesentery are mediated by nitric oxide. 856 31


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