Summary
We investigated the vasodilatory effect of intracisternal (i.c.) and intravenous (i.v.) administration of calcitonin gene-related peptide (CGRP) on arterial narrowing after experimental subarachnoid hemorrhage (SAH). Forty-one rabbits were divided into five groups: control (normal animals); SAH plus i.c. infusion of vehicle; SAH plus i.c. infusion of CGRP; SAH plus i.v. infusion of vehicle; SAH plus i.v. infusion of CGRP. In all but the control group, either CGRP (100ng/kg/min) or vehicle solution was infused for two hours immediately prior to sacrifice by perfusion-fixation. A morphometric technique was employed to measure the luminal diameter of rabbit basilar arteries two days after SAH. The diameter of the basilar arteries in either the i.c. or i.v. CGRP groups was significantly greater than that of the respective vehicle group (i.c., p < 0.001; i.v., p < 0.01). Although there was no significant difference in systemic arterial blood pressure after infusion between the i.c. vehicle and i.c. CGRP groups, i.v. CGRP caused significant hypotension. Our results suggest that exogenous CGRP has some therapeutic potential for arterial narrowing after SAH not only by intrathecal application, but also by systemic use.
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References
Boisvert DP, Overston TR, Weir B, Grace MG (1978) Cerebral arterial responses to induced hypertension following subarachnoid hemorrhage in the monkey. J Neurosurg 49: 75–83
DiPette DJ, Schwarzenberger K, Kerr N, Holland B (1987) Systemic and regional hemodynamic effect of calcitonin gene-related peptide. Hypertension 9 [Suppl III]: 142–146
Echlin F (1971) Experimental vasospasm, acute and chronic, due to blood in the subarachnoid space. J Neurosurg 35: 646–656
Edvinsson L, Delgado-Zygmunt T, Ekman R, Jansen I, Svendggaard NA, Uddman R (1990) Involvement of perivascular sensory fibers in the pathophysiology of cerebral vascular vasospasm following subarachnoid hemorrhage. J Cereb Blood Flow Metabol 10: 602–607
Fitch W, Pickard JW, Tamura A, Graham DI (1988) Effect of hypotension induced with sodium nitroprusside on the cerebral circulation before, and one week after, the subarachnoid injection of blood. J Neurol Neurosurg Psychiatry 51: 88–93
Gardiner SM, Compton AM, Bennett T (1989) Regional haemodynamic effect of α- and β-calcitonin gene-related peptide in conscious Wistar rats. Br J Pharmacol 98: 1225–1232
Hanko J, Hardebo JE, Kahrstrom J, Owman C, Sundler F (1985) Calcitonin gene-related peptide is present in mammalian cerebrovascular nerve fibers and dilates pial and peripheral arteries. Neurose Lett 57: 91–95
Hongo K, Tsukahara T, Kassell NF, Ogawa H (1989) Effect of subarachnoid hemorrhage on calcitonin gene-related peptideinduced relaxation in rabbit basilar artery. Stroke 20: 100–104
Johnston FG, Bell BA, Robertson IJA, Miller JD, Haliburn C, O'Laoire SA (1990) Effect of calcitonin-gene-related peptide on postoperative neurological deficits after subarachnoid haemorrhage. Lancet 335: 862–872
Kassell NF, Sasaki T, Colohan ART, Nazar G (1985) Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Stroke 16: 562–572
McCulloch J, Uddman R, Kingman TA, Edvinsson L (1986) Calcitonin gene-related peptide: functional role in cerebrovascular regulation. Proc Natl Acad Sci USA 83: 5731–5735
Mejia JA, Pernow J, Hoist HV, Rudehill A, Lundberg JM (1988) Effects of neuropeptide Y, calcitonin gene-related peptide, substance P, and cerebral arteries in man and animals. J Neurosurg 69: 913–918
Nakagomi T, Kassell NF, Hongo K, Sasaki T (1990) Pharmacological reversibility of experimental cerebral vasospasm. Neurosurgery 27: 582–586
Naylor AR, Robertson IJA, Edwards CRW, Merrick MV, Sellar RJ, O'Shaughnessy D, Miller JD (1991) Cerebral vasospasm following subarachnoid hemorrhage: effect of calcitonin generelated peptide on middle cerebral artery velocities using transcranial doppler sonography. Surg Neurol 36: 278–280
Nozaki K, Uemura Y, Okamoto S, Kikuchi H, Mizuno N (1989) Relaxant effect of calcitonin gene-related peptide on cerebral arterial spasm induced by experimental subarachnoid hemorrhage in dogs. J Neurosurg 71: 558–564
Nozaki K, Kikuchi H, Mizuno N (1989) Changes of calcitonin gene-related peptide-like immunoreactivity in cerebrovascular nerve fibers in the dog after experimentally produced subarachnoid hemorrhage. Neurosci Lett 102: 27–32
Pasqualin A, Vollmer DG, Marron JA, Tsukahara T, Kassell NF, Torner JC (1991) The effect of nicardipine on vasospasm in rabbit basilar artery after subarachnoid hemorrhage. Neurosurgery 29: 183–188
Rosenfield MG, Mermod JJ, Amara SG, Swanson LW, Sawchenko PE, River J, Vale WW, Evans RM (1983) Production of a novel neuropeptide encoded by calcitonin gene via tissuespecific RNA processing. Nature 304: 129–135
Salmon P, Fitzgerald D, Lambe R, Darragh A, O'Shaughnessy D, Riddell A, Ney U (1989) A single rising intravenous dose tolerance and pharmacodynamic study of human calcitonin gene related peptide (CGRP) in healthy male volunteers. Clin Pharmacol Ther 45: 170
Shibuya M, Suzuki Y, Takayasu M, Asano T, Harada T, Satoh S, Hidaka H (1988) The effects of an intracellular calcium antagonist HA 1077 on delayed cerebral vasospasm in dogs. Acta Neurochir (Wien) 90: 53–59
Struthers AD, Brown MJ, MacDonald DWR, Beacham JL, Stevenson JC, Morris HR, MacIntyre I (1986) Human calcitonin gene related peptide: A potent endogenous vasodilator in man. Clin Sci 70: 389–393
Takayasu M, Suzuki Y, Shibuya M, Asano T, Kanamori M, Okada T, Kageyama N, Hidaka H (1986) The effect of HA compound calcium antagonists on delayed cerebral vasospasm in dogs. J Neurosurg 65: 80–85
Uddman R, Edvinsson L, Ekblad E, Hakanson R, Sundler F (1986) Calcitonin gene-related peptide (CGRP) perivascular distribution and vasodilatory effect. Regul Pept 15: 1–23
Voldby B, Enevoldsen EM, Jensen FT (1985) Cerebrovascular reactivity in patients with ruptured intracranial aneurysms. J Neurosurg 62: 59–67
Vollmer DG, Jane JS, Torner JC, Kassell NF (1988) Intracisternal papaverine reverses experimental cerebral vasospasm in rabbit model. In: Wilkins RH (ed) Cerebral vasospasm. Raven Press, New York, pp 425–431
Wallenstein S, Zucker CL, Fleiss JL (1980) Some statistical methods useful in circulation research. Circ Res 47: 1–9
Wilkins RH (1986) Attempts at prevention or treatment of intracranial arterial spasm: an update. Neurosurgery 18: 808–825
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Toshima, M., Kassell, N.F., Tanaka, Y. et al. Effect of intracisternal and intravenous calcitonin gene-related peptide on experimental cerebral vasospasm in rabbits. Acta neurochir 119, 134–138 (1992). https://doi.org/10.1007/BF01541797
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DOI: https://doi.org/10.1007/BF01541797