Original Articles| Volume 12, ISSUE 2, P82-87, March 2003

Download started.


Plasma nitric oxide (nitrate/nitrite) levels in acute stroke and their relationship with severity and outcome


      Endothelium-derived nitric oxide is beneficial in experimental stroke. We assessed plasma NO levels in patients with acute stroke and their association with both severity and outcome. Plasma nitric oxide (NO), assessed as nitrate/nitrite (NOx), cyclic guanosine monophosphate (cGMP, second messenger to NO), L-arginine (substrate for NO) and L-citrulline (co-product with NO) levels were measured in 228 patients with acute ischemic stroke, 49 patients with acute hemorrhagic stroke, and 38 age and gender-matched normal volunteers. Stroke severity was assessed using the Glasgow Coma Scale, and the outcome was judged by discharge destination (home, institution, or dead). In our study, stroke patients had low levels of NOx (μmol/l): ischemic 49.9 (26.1); hemorrhage 41.7 (19.5); and control 64.0 (36.3) (P <.001); L-arginine (μmol/l): ischemic 85.1 (32.3); hemorrhage 69.9 (24.4); and control 104.0 (30.0) (P <.001); and L-citrulline (μmol/l): ischemic 30.5 (12.3); hemorrhage 26.7 (12.1); and control 39.4 (13.5) (P <.001). Cyclic GMP levels were elevated in stroke: ischemic 21.2 (16.1); hemorrhage 24.7 (17.5); and control 15.8 (9.2) (P =.024). Patients who died or became institutionalized had lower NOx, L-arginine, and L-citrulline levels, and higher cyclic GMP levels, than patients who were discharged home. NOx levels were not associated with feeding status in patients. Low levels of NOx are present in stroke and are associated with severity and outcome. Because endothelium-derived NO is beneficial in acute stroke, administering NO might be beneficial in acute stroke. Copyright © 2003 by National Stroke Association


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Stroke and Cerebrovascular Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Snyder SH
        • Bredt DS
        Biological roles of nitric oxide.
        Sci Am. 1992; 266 (, 74-77): 68-71
        • Lipton SA
        • Chol Y-B
        • Pan Z-H
        • et al.
        A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds.
        Nature. 1993; 364: 626-632
        • Dalkara T
        • Moskowitz MA
        The complex role of nitric oxide in the pathophysiology of focal cerebral ischemia.
        Brain Pathol. 1994; 4: 49-57
        • Samdani AF
        • Dawson TM
        • Dawson VL
        Nitric oxide synthase in models of focal ischemia.
        Stroke. 1997; 28: 1283-1288
        • Dawson DA
        Nitric oxide and focal cerebral ischemia: multiplicity of actions and diverse outcome.
        Cerebrovasc Brain Metab Rev. 1994; 6: 299-324
        • Huang Z
        • Huang PL
        • Ma J
        • et al.
        Enlarged infarcts in endothelial nitric oxide synthase knockout mice are attenuated by nitro-L-arginine.
        J Cereb Blood Flow Metab. 1996; 16: 981-987
        • Huang Z
        • Huang PL
        • Panahian N
        • et al.
        Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase.
        Science. 1994; 265: 1883-1885
        • Escott KJ
        • Beech JS
        • Haga KK
        • et al.
        Cerebroprotective effect of the nitric oxide synthase inhibitors, 1-(2-trifluoromethylphenyl) imidazole (TRIM) and 7-nitro indazole, after transient focal cerebral ischemia in the rat.
        J Cereb Blood Flow Metab. 1998; 18: 281-287
        • Cash D
        • Beech JS
        • Rayne RC
        • et al.
        Neuroprotective effect of aminoguanidine on transient focal ischaemia in the rat brain.
        Brain Res. 2001; 905: 91-103
        • Toprakci M
        • Ozmen D
        • Mutaf I
        • et al.
        Age-associated changes in nitric oxide metabolites nitrite and nitrate.
        Int J Clin Lab Res. 2000; 30: 83-85
        • Linder L
        • Kiowski W
        • Buhler FR
        • et al.
        Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo.
        Circulation. 1990; 81: 1762-1767
        • Creager MA
        • Cooke JP
        • Mendelsohn ME
        • et al.
        Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans.
        J Clin Invest. 1990; 86: 228-234
        • Zheng G
        • Chopp M
        • Zaloga C
        • et al.
        Cerebral endothelial nitric oxide synthase expression after focal cerebral ischemia in rats.
        Stroke. 1993; 24: 2016-2022
        • Kader A
        • Frazzini VI
        • Solomon RA
        • et al.
        Nitric oxide production during focal cerebral ischemia in rats.
        Stroke. 1993; 24: 1709-1716
        • Kumura E
        • Kosaka H
        • Shiga T
        • et al.
        Elevation of plasma nitric oxide end products during focal cerebral ischemia and reperfusion in the rat.
        J Cereb Blood Flow Metab. 1993; 14: 487-491
        • Bath PMW
        • Butterworth RJ
        • Soo J
        • et al.
        The King's College Hospital Acute Stroke Unit.
        J R Coll Physicians Lond. 1996; 30: 13-17
        • Bamford J
        • Sandercock P
        • Dennis M
        • et al.
        Classification and natural history of clinically identifiable subtypes of cerebral infarction.
        Lancet. 1991; 337: 1521-1526
        • Ferlito S
        • Gallina M
        • Pitari GM
        • et al.
        Nitric oxide plasma levels in patients with chronic and acute cerebrovascular disorders.
        Panminerva Med. 1998; 40: 51-54
        • Butterworth RJ
        • Cluckie A
        • Jackson SHD
        • et al.
        Pathophysiological assessment of nitric oxide (given as sodium nitroprusside) in acute ischemic stroke.
        Cerebrovasc Dis. 1998; 8: 158-165
        • Bath PMW
        • Pathansali R
        • Iddenden R
        • et al.
        The effect of transdermal glyceryl trinitrate, a nitric oxide donor, on blood pressure and platelet function in acute stroke.
        Cerebrovasc Dis. 2001; 11: 265-272
        • Zhang F
        • White JG
        • Iadecola C
        Nitric oxide donors increase blood flow and reduce brain damage in focal ischemia: evidence that nitric oxide is beneficial in the early stages of cerebral ischemia.
        J Cereb Blood Flow Metab. 1994; 14: 217-226
        • Bath PM
        Major ongoing stroke trials. Efficacy of Nitric Oxide in Stroke (ENOS) trial.
        Stroke. 2001; 32 (abstract): 2450-2451
        • Castillo J
        • Ramon R
        • Davalos A
        Nitric oxide-related brain damage in acute ischemic stroke.
        Stroke. 2000; 31: 852-857
        • Palmer GC
        Cyclic nucleotides in stroke and related cerebrovascular disorders.
        Life Sci. 1985; 36: 1995-2006
        • Estrada V
        • Tellez MJ
        • Moya J
        • et al.
        High plasma levels of endothelin-1 and atrial natriuretic peptide in patients with acute ischemic stroke.
        Am J Hypertens. 1994; 7: 1085-1090
        • Sander D
        • Klingelhofer J
        Stroke-associated pathological sympathetic activation related to size of infarction and extent of insular damage.
        Cerebrovasc Dis. 1995; 5: 381-385
        • Murros K
        • Fogelholm R
        • Kettunen S
        • et al.
        Serum cortisol and outcome of ischemic brain infarction.
        J Neurol Sci. 1993; 116: 12-17
        • Feibel JH
        • Hardy PM
        • Campbell RG
        • et al.
        Prognostic value of the stress response following stroke.
        JAMA. 1977; 238: 1374-1376
        • Rashid P
        • Bath P
        Plasma nitric oxide (nitrate) in stroke by type, severity and outcome.
        Stroke. 2000; 31 (abstract): 2835