Calcitonin gene-related peptide (human α-CGRP) counteracts vasoconstriction in human subarachnoid haemorrhage

Juul, Roar; Aakhus, Svend; Bjørnstad, Knut; Gisvold, Sven Erik; Brubakk, Alf O.; Edvinsson, Lars

doi:10.1016/0304-3940(94)90240-2

Cited by 64 publications

(42 citation statements)

References 12 publications

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“…In patients with subarachnoid hemorrhage, a CGRP-infusion concomitant with intravenous fluid to correct any drop in blood pressure resulted in a dilation of the MCA on the vasospasm side [25]. Blood pressure was unchanged while heart rate and cardiac output were increased and total peripheral resistance was decreased [25].…”

Section: Discussionmentioning

confidence: 99%

Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients

et al. 2008

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Calcitonin gene-related peptide (CGRP)-containing nerves are closely associated with cranial blood vessels. CGRP is the most potent vasodilator known in isolated cerebral blood vessels. CGRP can induce migraine attacks, and two selective CGRP receptor antagonists are effective in the treatment of migraine attacks. It is therefore important to investigate its mechanism of action in patients with migraine. We here investigate the effects of intravenous human alpha-CGRP (hαCGRP) on intracranial hemodynamics. In a double-blind, cross-over study, the effect of intravenous infusion of hαCGRP (2 μg/min) or placebo for 20 min was studied in 12 patients with migraine without aura outside attacks. Xenon-133 inhalation SPECT-determined regional cerebral blood flow (rCBF) and transcranial Doppler (TCD)-determined blood velocity (Vmean) in the middle cerebral artery (MCA), as well as the heart rate and blood pressure, were the outcome parameters. No change of rCBF was observed at the end of infusion [1.2% ± 1.7 with hαCGRP, vs. −1.6% ± 3.1 with placebo (mean ± SD)] (P = 0.43). Vmean in MCA decreased to 13.5% ± 3.6 with hαCGRP versus 0.6% ± 1.8 with placebo (P < 0.005). Since rCBF was unchanged, this indicates a dilation of the MCA. hαCGRP induced a decrease in MAP (12%) (P < 0.005) and an increase in heart rate (58%) (P < 0.0001). CGRP dilates cerebral arteries, but the effect is so small that it is unlikely to be the only mechanism of CGRP-induced migraine.

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Section: Discussionmentioning

confidence: 99%

Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients

et al. 2008

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“…This evidence has led to the concept that addition of CGRP may be beneficial in a condition that has proven hard to treat. A preliminary clinical trial with CGRP provided evidence for an ability of intravenously administered CGRP to reverse the vasoconstriction (174). However, this was not reflected in a multicenter clinical trial (18).…”

Section: A Cgrp and Cerebral Conditionsmentioning

confidence: 96%

Vascular Actions of Calcitonin Gene-Related Peptide and Adrenomedullin

Brain

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2004

Physiological Reviews

675

542

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This review summarizes the receptor-mediated vascular activities of calcitonin gene-related peptide (CGRP) and the structurally related peptide adrenomedullin (AM). CGRP is a 37-amino acid neuropeptide, primarily released from sensory nerves, whilst AM is produced by stimulated vascular cells, and amylin is secreted from the pancreas. They share vasodilator activity, albeit to varying extents depending on species and tissue. In particular, CGRP has potent activity in the cerebral circulation, which is possibly relevant to the pathology of migraine, whilst vascular sources of AM contribute to dysfunction in cardiovascular disease. Both peptides exhibit potent activity in microvascular beds. All three peptides can act on a family of CGRP receptors that consist of calcitonin receptor-like receptor (CL) linked to one of three receptor activity-modifying proteins (RAMPs) that are essential for functional activity. The association of CL with RAMP1 produces a CGRP receptor, with RAMP2 an AM receptor and with RAMP3 a CGRP/AM receptor. Evidence for the selective activity of the first nonpeptide CGRP antagonist BIBN4096BS for the CGRP receptor is presented. The cardiovascular activity of these peptides in a range of species and in human clinical conditions is detailed, and potential therapeutic applications based on use of antagonists and gene targeting of agonists are discussed.

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“…Endogenous αCGRP appears to be released and subsequently depleted in response to cerebral vasoconstriction after SAH, leading to the suggestion that exogenous αCGRP may be beneficial in managing DCI (14–16). Several animal studies and three human trials have investigated the effect of αCGRP on cerebral arteries after SAH with a view to administering αCGRP as a treatment for DCI (17–40). However, there has been no systematic summary assessing the efficacy of αCGRP in reducing cerebral vasospasm in animal models.…”

Section: Introductionmentioning

confidence: 99%

Alpha Calcitonin Gene-Related Peptide Increases Cerebral Vessel Diameter in Animal Models of Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis

et al. 2017

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Delayed cerebral ischemia (DCI) is a life-threatening complication after subarachnoid hemorrhage. There is a strong association between cerebral vessel narrowing and DCI. Alpha calcitonin gene-related peptide (αCGRP) is a potent vasodilator, which may be effective at reducing cerebral vessel narrowing after subarachnoid hemorrhage (SAH). Here, we report a meta-analysis of data from nine in vivo animal studies identified in a systematic review in which αCGRP was administered in SAH models. Our primary outcome was change in cerebral vessel diameter and the secondary outcome was change in neurobehavioral scores. There was a 40.8 ± 8.2% increase in cerebral vessel diameter in those animals treated with αCGRP compared with controls (p < 0.0005, 95% CI 23.7–57.9). Neurobehavioral scores were reported in four publications and showed a standardized mean difference of 1.31 in favor of αCGRP (CI −0.49 to 3.12). We conclude that αCGRP reduces cerebral vessel narrowing seen after SAH in animal studies but note that there is insufficient evidence to determine its effect on functional outcomes.

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Calcitonin gene-related peptide (human α-CGRP) counteracts vasoconstriction in human subarachnoid haemorrhage

Cited by 64 publications

References 12 publications

Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients

Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients

Vascular Actions of Calcitonin Gene-Related Peptide and Adrenomedullin

Alpha Calcitonin Gene-Related Peptide Increases Cerebral Vessel Diameter in Animal Models of Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis

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