A Comparative Analysis of the Effects of Melatonin and Nimodipine on Vasospasm

J Clin Exp Invest 2018;9(3):113-118.



Download Full Text (PDF)


Objective: In this study, we aimed to compare the efficacy of nimodipine and melatonin in a rat femoral artery vasospasm model.
Material and Methods: The rats were divided into five groups as follows: Group I (n=8): control group, Group II (n=8): vasospasm group, Group III (n=8): vasospasm + melatonin group, Group IV (n=8): vasospasm + nimodipine group, Group V (n=8 rats): vasospasm + melatonin + nimodipine group. At the end of the 7th day, the femoral arteries were excised and histopathologically examined under light microscope.
Results: Vascular wall of vasospasm group was relatively thicker when compared with the control group. There was a statistically significant difference between the wall thickness of Group II and Group III, IV and V. The maximum reduction of wall thickness was observed in Group V. There was no statistically significant difference in lumen diameter between Group I and Group IV. The lumen diameter was found to be increased in Group III, IV and V when compared with Group II.
Conclusion: The development of experimental peripheral vasospasm has been reduced by the melatonin and nimodipine and their effect was increased when they were used concomitantly.


Melatonin, Nimodipine, Cerebral vasospasm, Rat femoral artery, Subarachnoid hemorrhage


  • Karaoglan A, Akdemir O, Barut S, et al. The effects of resveratrol on vasospasm after experimental subarachnoidal hemorrhage in rats. Surgical Neurology 2008;70:337-43.
  • Kemaloglu S, Ozkan U, Yilmaz F, et al. Preventive effects of intracisternal alphatochopherol on cerebral vasospasm in experimental subarachnoid haemorrhage. Yonsei Med J 2003;44:955-60.
  • Loch Macdonald RL. Management of cerebral vasospasm. Neurosurg Rev 2006;29:179-93.
  • Megyesi JF, Vollrath B, Cook DA, Findlay JM. In vivo animal models of cerebral vasospasm: a review. Neurosurgery 2000;46:448-60.
  • Allegra M, Reiter RJ, Tan DX, Gentile C, Tesoriere L, Livrea MA. The chemistry of melatonin’s interaction with reactive species. J Pineal Res 2003;34:1-10.
  • Reiter RJ, Tan DK, Manchester LC. Antioxidative capacity of melatonin. In: Cadenas E, Packer L (eds) Handbook of antioxidants. Marcel Dekker, New York, pp 2002;565-613.
  • Reiter Rj, Tan DX, Manchester LC, Qi W. Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence. Cell Biochem Biophys 2001;34:237-56.
  • Tan DX, Reiter RJ, Manchester LC, et al. Chemical and physical properties and potential mechanisms: melatonin as a broadspectrum antioxidant and free radical scavenger. Curr Top Med Chem 2002;2:181-97.
  • Okada T, Harada T, Bark DH, Mayberg MR. A rat femoral artery model for vasospasm. Neurosurgery 1990;27:349-56.
  • Kanamaru K, Weir BK, Findlay JM, Grace M, Macdonald RL. A dosage study of the effect of the 21-aminosteroid U74006F on chronic cerebral vasospasm in a primate model. Neurosurgery 1990;27:29-38.
  • McNeish AJ, Altayo FJ, Garland CJ. Evidence both L-type and non L-type voltage-dependent calcium channels contribute to cerebral artery vasospasm following loss of NO in the rat. Vascular Pharmacology 2010;53:151-59.
  • Christopher G, Harrod MS, Bernard R. Prediction of cerebral vasospasm in patients presenting with aneurysmal subarachnoid hemorrhage: a review. Neurosurgery 2005;56:633-52.
  • Kassell NF, Shaffrey M, Shaffrey C. Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. In Apuzzo M, editor. Brain Surgery p. 1993;847-56.
  • Liu S, Tang J, Ostrowski RP, et al. Oxidative stress after subarachnoid hemorrhage in gp91phox knockout mice. Can J Neurol Sci 2007;34:356- 61.
  • Silva SO, Rodriques MR, Carvalho SH, Catalani LH, Campa A, Ximenes VF. Oxidation of melatonin and its catabolites, N1-acetyl-N2-formyl-5- methoxykynuramine and N1-acetyl-5-methoxykynuramine, by activated leukocytes. J Pineal Res 2004;37:171-5.
  • Samantaray S, Das A, Thakore NP, et al. Therapeutic potential of melatonin in traumatic central nervous system injury. J Pineal Res 2009;47:134-42.
  • McGirt MJ, Parra A, Sheng H, et al. Attenuation of cerebral vasospasm after subarachnoid hemorrhage in mice overexpressing extracellular superoxide dismutase. Stroke 2002;33:2317-23.
  • Esposito E and Cuzzocrea S. Anti-inflammatory activity of melatonin in central nervous system. Current Neuropharmacology 2010;8:228-42.
  • Reiter RJ. Pineal melatonin cell biology of its synthesis and of its interactions. Endocr Rev 1991;12:151-80.
  • Kaptanoglu E, Palaoglu S, Demirpence E, Akbiyik F, Solaroglu I, Kilinc A. Different responsiveness of central nervous system tissues to oxidative conditions and to the antioxidant effect of melatonin. J. Pineal Res 2003;34:32-5.
  • Macdonald RL, Weir BK. Cerebral vasospasm and free radicals. Free Radic Biol Med 1994;16:633-43.
  • Guney O, Erdi F, Esen H, Kiyici A, Kocaogullar Y. N-acetylcysteine prevents vasospasm after subarachnoid hemorrhage. World Neurosurgery 2009;73:42-9.
  • Naredi S,Lambert G, Eden E. Increased sympathetic nervous activity in patients with nontraumatic subarachnoid hemorrhage. Stroke 2000;31:901-6.
  • Mayberg MR, Okada T, Bark DH. The role of hemoglobin in arterial narrowing after subarachnoid hemorrhage. J Neurosurg 1990;72:634-40.
  • Radogna F, Nuccitelli S, Mengoni F, Ghibelli L. Neuroprotection by melatonin on astrocytoma cell death. Ann NY Acad Sci 2003;1171:509-13.
  • Triggle DJ. Calcium channel antagonists: clinical uses- past, present and future. Biochem Pharmacol 2007;74:1-9.
  • Antolin I, Rodriguez C, Sainz RM, et al. Neurohormone melatonin prevents cell damage: effect on gene expression for antioxidant enzymes. FASEB J 1999;10:882-90.
  • Genova ML, Pich MM, Biondi A, et al. Mitochondrial production of oxygen radical species and the role of Coenzyme Q as an antioxidant. Exp Biol Med (Maywood) 2003;228:506-13.
  • Rothoerl RD, Ringel F. Molecular mechanisms of cerebral vasospasm following aneurysmal SAH. Neurol Res 2007;29:636-42.
  • Skene DJ, Lockley SW, Arendt J. Use of melatonin in the treatment of phase shift and sleep disorders. Adv Exp Med Biol 1999;467:79-84.
  • Aladag MA, Turkoz Y, Sahna E, Parlakpinar H, Gul M. The attenuation of vasospasm by using a sod mimetric after experimental subarachnoidal haemorrhage in rats. Acta Neurochir (Wien) 2003;145:673-7.
  • Aladag MA, Turkoz Y, Parlakpinar H, Ozen H, Egri M, Unal SC. Melatonin ameliorates cerebral vasospasm after experimental subarachnoidal haemorrhage correcting imbalance on nitric oxide levels in rats. Neurochem Res 2009;34:1935-44.
  • Reiter RJ, Carneiro RC, Oh C-S. Melatonin in relation to cellular antioxidative defense mechanisms. Horm Metab Res 1997;29:363-72.
  • Reiter RJ, Tan D-X, Manchester LC, Tamura H. Melatonin defeats neurally-derived free radicals and reduces the associated neuromorphological and neurobehavioral damage. J Physiol and Pharmacol 2007;58:5-22.
  • Siesjö BK. Calcium and ischemic brain damage. Eur Neurol 1986;25:44- 56.
  • Acuna-Castroviejo D, Martin M, Macias M, et al. Melatonin, mitochondria, and cellular bioenergetics. J Pineal Res 2001;30:65-70.
  • Perez-Reyes E. Molecular physiology of low-voltage-activated t-type calcium channels. Physiol Rev 2003;83:117-61.
  • Tan DX, Manchester LC, Reiter RJ, Qi WB, Karbownik M, Calvo JR. Significance of melatonin in antioxidative defense: reactions and products. Biol Signals Recept 2000;9:137-59.
  • Eskiocak S, Tutunculer F, Basaran UN, Taskiran A, Cakir E. The effect of melatonin on protein oxidation and nitric oxide in the brain tissue of hypoxic neonatal rats. Brain&Development 2007;29:19-24.
  • Reiter RJ. Melatonin lowering the high price of free radicals. News Physiol Sci 2000;15:246-50.
  • Samantaray S, Sribnick EA, Das A, et al. Melatonin attenuates calpain upregulation, axonal damage and neuronal death in spinal cord injury in rats. J Pineal Res 2008;44:348-57.
  • Samel A. Melatonin and jet-lag. Eur J Med Res 1999;4:385-8.


Akar E, Batçık KE, Acar C, Ton Ö, Canaz H, Baydın S, et al. A Comparative Analysis of the Effects of Melatonin and Nimodipine on Vasospasm. J Clin Exp Invest. 2018;9(3):113-8. https://doi.org/10.5799/jcei.458757