Calcitonin gene-related peptide vasodilation of human pulmonary vessels

McCormack, David G.; Mak, Judith C.W.; Coupe, Michael; Barnes, Peter J.

doi:10.1152/jappl.1989.67.3.1265

Cited by 91 publications

(36 citation statements)

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“…This is despite there being ample literature on ADM-binding sites on vascular smooth muscle cells in culture and their functional coupling to the cAMP system (Eguchi et al 1994;Horio et al 1995). There is also similar published evidence of functional CGRP receptors on human vascular smooth muscle (Luu et al 1995;McCormack et al 1989). We therefore believe that CRLR levels in vascular smooth muscle cells in situ have been close to the detection limit of our immunohistochemistry.…”

Section: Discussionmentioning

confidence: 54%

Calcitonin receptor-like receptor: identification and distribution in human peripheral tissues

Hagner

Stahl

Knoblauch

et al. 2002

Cell and Tissue Research

108

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We report here on the characterization and immunohistochemical localization in human tissues of calcitonin receptor-like receptor (CRLR) which was recently found to mediate the effects of both calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM). Western blot analysis using antibodies raised against the first extracellular loop and the carboxy-terminal part of hCRLR, respectively, detected two major bands corresponding to about 70 and 60 kDa in membrane preparations of cultured endothelial cells and numerous organs including lung, heart ventricle and kidney. Immunohistochemical analysis of the cardiovascular system revealed CRLR-like immunoreactivity (CRLR-LI) in the endothelium of all blood vessels including large and small arteries, veins and capillaries, and in heart muscle cells and endocardium. The lung showed intense staining over the alveolar capillaries. Within the digestive tract, staining was observed over the cells lining the excretory ducts of the parotid gland, over the epithelium of the fundic glands of stomach, endocrine cells of the duodenum and ileum and some myenteric ganglia. The kidney presented staining of the juxtaglomerular arteries, the glomerular capillaries and chief cells of the collecting duct. Within the endocrine organs, a strong CRLR-LI signal was observed over the Langerhans islets, and weak immunoreactivity in the Leydig cells of testis. Spleen showed intense staining in trabecular veins and sinuses. Macrophages displayed a variable immunoreactivity. Our data demonstrate a wide distribution of CRLR throughout the human body and suggest CRLR to be involved in the mediation of a variety of actions in addition to vascular control.

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Section: Discussionmentioning

confidence: 54%

Calcitonin receptor-like receptor: identification and distribution in human peripheral tissues

Hagner

Stahl

Knoblauch

et al. 2002

Cell and Tissue Research

108

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“…Many investigators have demonstrated that CGRP does not require intact endothelium for a vasodilatory action in human pial arteries (11,12); rabbit, cat, canine, and pig cerebral arteries (11)(12)(13)(14)(15); rabbit and cat mesenteric arteries (11); porcine and bovine coro nary arteries (16,17); human pulmonary arteries and veins (18); pig splenic and human skeletal muscle arter ies (19); and rat gastric, splenic, and hepatic arteries (20). However, little is known about the effects of the endothelium on the vascular reactivity to CGRP of rat cerebral arteries.…”

Section: Discussionmentioning

confidence: 99%

Relaxant Response of Isolated Basilar Arteries to Calcitonin Gene-Related Peptide in Stroke-Prone Spontaneously Hypertensive Rats.

et al. 1992

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ABSTRACT-The relaxant effects of calcitonin gene-related peptide (CGRP) and other drugs were compared in basilar artery rings obtained from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY). In addition, the relaxant effect of CGRP on basilar arteries from spon taneously hypertensive rats (SHR) was examined. Relaxation induced by CGRP was independent of the presence of endothelium, and it was markedly increased in SHRSP when compared to WKY. In contrast, acetylcholine-induced relaxation was endothelium-dependent and did not differ between the two groups. Enhanced CGRP-induced relaxation was also found in SHR when compared to WKY. However, the relaxant response was greater in SHRSP than in SHR. No significant differences were found in the relaxation induced by isoproterenol, forskolin, dibutyryl cyclic AMP, and 3-isobutyl-l methylxanthine in endothelium-rubbed arteries of WKY and SHRSP. These results suggest that CGRP produces endothelium-independent relaxation in the rat basilar artery, and that the enhanced CGRP induced relaxation found in SHRSP may not be associated with alterations of vasodilation mediated by cyclic AMP.Keywords: Calcitonin gene-related peptide (CGRP), Stroke-prone spontaneously hypertensive rats (SHRSP), Basilar artery, Vascular relaxation, Endothelium Calcitonin gene-related peptide (CGRP), translated from the calcitonin gene (1, 2), has been shown to be a potent vasodilator and to have a role in the regulation of both peripheral and cerebral vascular tone (3-5).It is well-documented that hypertension produces functional and morphological changes of the peripheral and cerebral vascular beds. Thus, an altered vascular response to CGRP would be expected in hypertensive animal models. It was recently demonstrated that the vasodilatory response to exogenously applied CGRP was significantly increased in spontaneously hyperten sive rats (SHR) when compared to Wistar-Kyoto rats (WKY), whereas no significant difference was found between rats with deoxycorticosterone-salt-induced hypertension and normotensive Wistar rats, in studies using isolated perfused mesenteric vascular beds (6, 7). However, there is little information available about the vascular response to CGRP in the cerebral arteries of hypertensive animals.In the present study, to determine whether cerebro vascular reactivity to CGRP was altered in hypertensive animal models, we examined the responses to CGRP and other drugs of isolated basilar arteries obtained from stroke-prone spontaneously hypertensive rats (SHRSP) (8). In addition, we examined the vascular re sponse of SHR basilar arteries to CGRP. MATERIALS AND METHODS AnimalsMale WKY, SHRSP, and SHR aged 6-7 months were used. Body weight was 356.2 ± 8.6 g (n = 20), 304.1 ± 5.8 g (n = 21), 373.8 ± 12.6 g (n = 4) for the WKY, SHRSP and SHR, respectively. Systolic blood pressure was measured by the standard tail cuff method; it was 144.3 ± 2.1 mmHg (n = 20), 225.5 ± 4.2 mmHg (n = 21), and 201.5 ± 8.5 mmHg (n = 4) for the WKY, SHRSP, and SHR groups, resp...

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“…Our study has demonstrated that CGRP acts directly on the smooth muscle via specific receptors to produce relax 97 ation in human epicardial coronary arteries. This mecha nism has been shown in many vascular beds, including human pial and pulmonary arteries [16,17]. In contrast there is evidence for other mechanisms of action for CGRP in animal and human tissue.…”

Section: Discussionmentioning

confidence: 86%

Calcitonin Gene-Related Peptide in Healthy and Atheromatous Human Epicardial Coronary Arteries

Luu

Dashwood²,

Chester³

et al. 1995

J Vasc Res

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To examine the possible role of calcitonin gene-related peptide (CGRP) in the control of human coronary vascular tone, we have investigated the action of this peptide in healthy and atheromatous human epicardial coronary arteries and localised [¹²⁵I]CGRP-binding sites in these vessels. Isolated arteries were obtained from 10 cardiomyopathic patients and 6 patients with ischaemic heart disease (IHD), who were undergoing heart transplantation. CGRP elicited concentration-dependent vasodilatation in preconstricted vessels. Both healthy and diseased coronary arteries exhibited similar maximum responses and sensitivity to this peptide. Removal of the endothelium did not diminish the vasodilator action of CGRP in non-atherosclerotic coronary arteries. [¹²⁵I]CGRP bound to tissue sections in a concentration-dependent manner. Binding was similar in healthy and atheromatous vessels, with a B_max value of 10.2 ± 5.6 and 18.9 ± 3.0 amol/mg protein, and dissociation constant (K_d) of 0.07 ± 0.1 and 0.18 ± 0.1 nM, respectively. Dense [¹²⁵I]CGRP binding was mainly associated with vascular smooth muscle cells of both normal and diseased vessels with some patches of binding to regions of atherosclerotic plaque in vessels from patients with IHD. These data indicate that CGRP is a potent endothelium-independent vasodilator in the human coronary vasculature. The preservation of dilator function and CGRP receptor binding in atherosclerotic coronary arteries suggests that this peptide may play a role in the control or maintenance of vascular tone in certain disease states.

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Calcitonin gene-related peptide vasodilation of human pulmonary vessels

Cited by 91 publications

References 0 publications

Calcitonin receptor-like receptor: identification and distribution in human peripheral tissues

Calcitonin receptor-like receptor: identification and distribution in human peripheral tissues

Relaxant Response of Isolated Basilar Arteries to Calcitonin Gene-Related Peptide in Stroke-Prone Spontaneously Hypertensive Rats.

Calcitonin Gene-Related Peptide in Healthy and Atheromatous Human Epicardial Coronary Arteries

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