Relaxant effect of calcitonin gene-related peptide on cerebral arterial spasm induced by experimental subarachnoid hemorrhage in dogs

1989 ◽  
Vol 71 (4) ◽  
pp. 558-564 ◽  
Author(s):  
Kazuhiko Nozaki ◽  
Yoshihiko Uemura ◽  
Shinichiro Okamoto ◽  
Haruhiko Kikuchi ◽  
Noboru Mizuno
Keyword(s):  
Body Weight ◽  
Subarachnoid Hemorrhage ◽  
Single Injection ◽  
Cerebral Arteries ◽  
Arterial Spasm ◽  
Relaxant Effect ◽  
Double Injection ◽  
Related Peptide ◽  
Injection Model ◽  
Calcitonin Gene

✓ This study examines the relaxant effect of calcitonin gene-related peptide (CGRP), a 37-amino acid peptide with a potent vasodilator action, on cerebral arterial spasm after subarachnoid hemorrhage (SAH). The spasm was induced by injecting autologous arterial blood percutaneously into the cisterna magna in adult mongrel dogs. The single-injection model of SAH was produced by injection of 1.0 ml/kg body weight of blood (on Day 0), and the double-injection model involved two successive injections of 0.5 ml/kg body weight of blood made 48 hours apart (on Day 0 and Day 2). On vertebral angiograms, arterial narrowing of the major cerebral arteries was most prominent on Day 3 after SAH in the single-injection model and on Day 7 in the double-injection model. When 10−10 mol/kg of CGRP was administered intracisternally in the single-injection model on Day 3, the diameter of the spastic cerebral arteries, as determined by angiography, recovered to normal. After intracisternal administration of 10−11 to 2 × 10−10 mol/kg of CGRP on Day 7 in double-injection models, spastic cerebral arteries dilated in a dose-dependent manner. The dilatory effect of CGRP continued for a few hours after administration. The results suggest that CGRP injected intracisternally may reverse cerebral arterial spasm after SAH.

Vascular relaxation properties of calcitonin gene-related peptide and vasoactive intestinal polypeptide in subarachnoid hemorrhage

1990 ◽  
Vol 72 (5) ◽  
pp. 792-797 ◽  
Author(s):  
Kazuhiko Nozaki ◽  
Shinichiro Okamoto ◽  
Yoshihiko Uemura ◽  
Haruhiko Kikuchi ◽  
Noboru Mizuno
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Vasoactive Intestinal Polypeptide ◽  
Basilar Artery ◽  
Single Injection ◽  
Calcitonin Gene Related Peptide ◽  
Vascular Relaxation ◽  
Double Injection ◽  
Related Peptide ◽  
Injection Model ◽  
Calcitonin Gene

✓ The vascular relaxation effects of calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) on the dog basilar artery after experimentally produced subarachnoid hemorrhage (SAH) were examined in vitro by an isometric tension recording method. Both CGRP and VIP induced dose-dependent relaxations in ring segments of the intact basilar artery of control dogs. The vasorelaxant action of CGRP was more potent than that of VIP. The single-injection model of SAH was produced by injection of fresh autologous arterial blood ( 1 ml/kg body weight) into the cisterna magna on Day 0 of the post-SAH period, and the double-injection model was produced by two injections of blood (0.5 ml/kg each) on Days 0 and 2. Narrowing of the basilar arteries on vertebral angiograms was most prominent on Day 3 or 7 in the single- or double-injection model, respectively. Relaxation of the basilar artery induced by CGRP and VIP was to some extent decreased on Days 3 and 7 of the post-SAH period in the single-injection model, and on Days 7 and 14 in the double-injection model. However, the vasorelaxant effects of CGRP and VIP were significantly enhanced on Day 14 of the post-SAH period in the single-injection model, and on Days 28 and 42 in the double-injection model. Subsequently, these effects returned to control levels by Days 28 or 63 in the single- or double-injection model, respectively.

Effects of subarachnoid hemorrhage on vascular responses to calcitonin gene—related peptide and its related second messengers

1995 ◽  
Vol 83 (3) ◽  
pp. 516-521 ◽  
Author(s):  
Bernhard Sutter ◽  
Satoshi Suzuki ◽  
Adam S. Arthur ◽  
Neal F. Kassell ◽  
Kevin S. Lee
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Second Messengers ◽  
Second Messenger ◽  
Relaxant Effect ◽  
Content Type ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Second Messenger Systems ◽  
Fine Print

✓ Calcitonin gene—related peptide (CGRP) is a potent vasodilator and a primary signaling molecule in neurovascular communication. In the present study, the authors examined cerebrovascular responses to CGRP and its related second messenger systems during cerebral vasospasm induced by subarachnoid hemorrhage (SAH). Tension measurements were performed in vitro on ring strips of basilar arteries obtained from rabbits subjected to artificial SAH and from control (non-SAH) animals. In vessels from SAH animals, which were preconstricted with serotonin, the vasorelaxant response to CGRP was attenuated. Because it has been suggested that vasodilation elicited by CGRP is mediated by cyclic 3′,5′-adenosine monophosphate (cAMP) and/or cyclic 3′,5′-guanosine monophosphate (cGMP), the vascular effects of directly activating these second messenger systems were also examined. The relaxant effect of forskolin, which activates adenylate cyclase directly, was slightly enhanced after SAH. In contrast, the relaxant effect of nitroglycerin (GTN), which activates soluble guanylate cyclase directly, was unchanged after SAH. The attenuation of CGRP-induced vasorelaxation could be the result of a modification in its ability to stimulate the production of second messengers. Experiments testing the capacity of CGRP to elevate cAMP levels showed no significant differences between vessels from non-SAH and SAH animals. Similarly, the resting levels of cAMP and the forskolin-induced elevations of cAMP did not differ between non-SAH and SAH animals. In contrast, cGMP levels were lower in resting and CGRP-treated vessels from SAH animals than in those from non-SAH animals. No significant differences in the levels of cGMP were observed between non-SAH and SAH vessels treated with GTN. This study indicates that CGRP-induced vasodilation is attenuated during vasospasm in a rabbit model of SAH. The findings also demonstrate that vasodilatory responses mediated by cAMP and cGMP are intact, although the levels of cGMP in SAH vessels are reduced. Together, these observations suggest that an attenuation in the capacity of vessels to dilate in response to CGRP occurs during cerebral vasospasm, and this change in CGRP vasoactivity is a result of modifications prior to, or independent of, the elevation of cyclic nucleotide second messengers.

Effects of neuropeptide Y, calcitonin gene-related peptide, substance P, and capsaicin on cerebral arteries in man and animals

1988 ◽  
Vol 69 (6) ◽  
pp. 913-918 ◽  
Author(s):  
Juan Armando Mejia ◽  
John Pernow ◽  
Hans von Holst ◽  
Anders Rudehill ◽  
Jan M. Lundberg
Keyword(s):  
Substance P ◽  
Neuropeptide Y ◽  
Muscle Tone ◽  
Cerebral Arteries ◽  
Calcitonin Gene Related Peptide ◽  
Sensory Nerves ◽  
Pial Arteries ◽  
Relaxant Effect ◽  
Related Peptide ◽  
Calcitonin Gene

✓ The smooth-muscle tone of pial, middle, and anterior cerebral arteries from humans, cats, and pigs, respectively, was studied in vitro with respect to the effects of capsaicin and various peptides which are present in local perivascular nerves. Neuropeptide Y (NPY) caused concentration-dependent, potent contractions of the cerebral vessels both in the presence and in the absence of endothelium. In contrast to the response to noradrenaline (NA) and K+, the NPY effect was not altered by changes in the extracellular Ca++ concentration. The relaxant action of the calcium antagonist nifedipine on NPY-evoked contraction of cerebral arteries was not inhibited by a Ca++-deficient medium or by a high-Ca++ medium. Calcitonin gene-related peptide (CGRP), substance P (SP), and capsaicin caused relaxation of precontracted cerebral arteries with an intact endothelium. Calcitonin gene-related peptide was the most potent dilatory agent, and removal of the endothelium did not change the CGRP response. In contrast, the ability of SP to cause relaxation was abolished after removal of the endothelium. Capsaicin, which activates sensory nerves, induced long-lasting relaxation in both the presence and absence of endothelium. In conclusion, in contrast to earlier reported data, the contractile effect of NPY seems to be largely independent of extracellular Ca++, while NA- and K+-induced contractions are dependent on extracellular Ca++. The present results suggest that the relaxant effect of nifedipine on cerebral blood vessels may involve actions other than inhibition of Ca++ influx. The relaxant effect of capsaicin is likely to be induced by release of CGRP rather than SP. The potent effects of these peptides on human pial arteries suggest that neuropeptides may be involved in the control of cerebral blood flow in man.

Changes of neuropeptide immunoreactivity in cerebrovascular nerve fibers after experimentally produced SAH

1987 ◽  
Vol 66 (5) ◽  
pp. 741-747 ◽  
Author(s):  
Yoshihiko Uemura ◽  
Tetsuo Sugimoto ◽  
Shinichiro Okamoto ◽  
Hajime Handa ◽  
Noboru Mizuno
Keyword(s):  
Body Weight ◽  
Subarachnoid Hemorrhage ◽  
Substance P ◽  
Unit Area ◽  
Single Injection ◽  
Nerve Fibers ◽  
The Other ◽  
Content Type ◽  
Arterial Blood ◽  
Fine Print

✓ The immunoreactivity of vasoactive intestinal polypeptide (VIP)-, substance P (SP)-, and neuropeptide Y (NPY)-containing nerve fibers in the basilar artery (BA) and proximal portion of the middle cerebral artery (M1) was immunohistochemically examined in the dog after experimentally produced subarachnoid hemorrhage (SAH). The SAH was produced by a single injection of fresh autologous arterial blood (1 ml/kg body weight) into the cisterna magna. The density (the averaged number of nerve fibers in a unit area) of VIP-, SP-, and NPY-immunoreactive perivascular nerve fibers in the M1 segment and the BA was markedly decreased (5% to 40% of the normal value) immediately after the injection. The density of VIP- and SP-immunoreactive perivascular fibers increased 2 or 3 weeks after SAH and became normal by the 63rd day after injection. On the other hand, no substantial recovery was observed in the density of NPY-immunoreactive perivascular fibers by 63 days after injection.

Cyclooxygenase Inhibitors Modify the Relaxant Effect of Vasoactive Intestinal Polypeptide and Substance P in Isolated Porcine Ophthalmic Artery

Cephalalgia ◽  
1992 ◽  
Vol 12 (1) ◽  
pp. 15-19 ◽  
Author(s):  
Maurice B Vincent
Keyword(s):  
Substance P ◽  
Ophthalmic Artery ◽  
Calcitonin Gene Related Peptide ◽  
Cyclooxygenase Inhibitors ◽  
Plasma Extravasation ◽  
Relaxant Effect ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Ophthalmic Arteries

The absolute indomethacin effect in some unilateral headaches may, at least partially, be cyclooxygenase inhibition-independent. Aspirin and indomethacin, for example, may inhibit the neurogenically induced plasma extravasation in rat dura mater. Given the putative involvement of trigeminal neuropeptides in the pathophysiology of these conditions, the influence of cyclooxygenase inhibitors (indomethacin, acetylsalicylic acid (ASA) and naproxen) has been studied upon substance P, calcitonin gene-related peptide and vasoactive intestinal peptide (VIP)-induced vasodilatation in PGF2a precontracted porcine ophthalmic arteries in vitro. None of the cyclooxygenase inhibitors significantly altered the effects of calcitonin gene-related peptide. The 10-10 mol/1 VIP-induced relaxation was inhibited significantly by all three cyclooxygenase inhibitors. Substance P-induced relaxation (from 10-10 to 10-8 mol/l) was enhanced by ASA and inhibited both by naproxen and, to a lesser extent, by indomethacin. The results suggest mainly that VIP-induced relaxations, particularly at lower concentrations, may be inhibited by all three cyclooxygenase inhibitors, and that naproxen, to a greater extent than aspirin or indomethacin, showed a tendency to inhibit vasodilatation induced by all peptides.

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