Role of Nitric Oxide in Regulating Cerebrocortical Oxygen Consumption and Blood Flow during Hypercapnia

The effect of the nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) on the response of cerebrocortical oxygen consumption (CMRO2) and blood flow (CBF) to two levels of hypercapnia (Paco2 ∼ 60 mm Hg and Paco2 ∼ 90 mm Hg) was investigated in ketamine-anesthetized rats. CBF was calculated using the Kety–Schmidt approach and CMRO2 was calculated from the product of CBF and the arteriovenous (superior sagittal sinus) difference for oxygen. l-NAME treatment did not have a significant effect on either CMRO2 or CBE under normocapnic conditions but inhibited the hypercapnic increase of CMRO2 and the hypercapnic increase in CBF. These results suggest that NO plays a role in the response of CMRO2 and CBF during hypercapnia and are consistent with the suggestion that at least part of the increase in CBF observed during hypercapnia is coupled to an increase in CMRO2.

[1]  S. Kety,et al.  THE NITROUS OXIDE METHOD FOR THE QUANTITATIVE DETERMINATION OF CEREBRAL BLOOD FLOW IN MAN: THEORY, PROCEDURE AND NORMAL VALUES. , 1948, The Journal of clinical investigation.

[2]  R. Albrecht,et al.  Nitric Oxide Synthesis and Regional Cerebral Blood Flow Responses to Hypercapnia and Hypoxia in the Rat , 1993, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[3]  C. Iadecola,et al.  Does nitric oxide mediate the increases in cerebral blood flow elicited by hypercapnia? , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Z Benyó,et al.  Effects of NG‐nitro‐L‐arginine and L‐arginine on regional cerebral blood flow in the cat. , 1992, The Journal of physiology.

[5]  N. Lassen,et al.  Effect of Nitric Oxide Blockade by NG-Nitro-l-Arginine on Cerebral Blood Flow Response to Changes in Carbon Dioxide Tension , 1992, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[6]  A. McLaughlin,et al.  Significance of an opiate mechanism in the adjustment of cerebrocortical oxygen consumption and blood flow during hypercapnic stress , 1992, Brain Research.

[7]  B. Siesjö,et al.  Glucose consumption in rat cerbral cortex in normoxia, hypoxia and hypercapnia. , 1976, Acta physiologica Scandinavica.

[8]  Role of nitric oxide in neurally induced cerebroarterial relaxation. , 1991, The Journal of pharmacology and experimental therapeutics.

[9]  S H Snyder,et al.  Nitric oxide: first in a new class of neurotransmitters. , 1992, Science.

[10]  J. Patterson,et al.  Local Mechanism of CO2 Action on Cat Pial Arterioles , 1977, Stroke.

[11]  H. Saito,et al.  A central nervous system action of nitric oxide in blood pressure regulation. , 1992, The Journal of pharmacology and experimental therapeutics.

[12]  N. Toda,et al.  Possible role of nitric oxide in transmitting information from vasodilator nerve to cerebroarterial muscle. , 1990, Biochemical and biophysical research communications.

[13]  R. Veech,et al.  DECREASED RATE OF GLUCOSE UTILIZATION BY RAT BRAIN IN VIVO AFTER EXPOSURE TO ATMOSPHERES CONTAINING HIGH CONCENTRATIONS OF CO2 , 1975, Journal of neurochemistry.

[14]  S. Gardiner,et al.  The influence of atropine and atenolol on the cardiac haemodynamic effects of NG‐nitro‐l‐arginine methyl ester in conscious, Long Evans rats , 1992, British journal of pharmacology.

[15]  W. Dietrich,et al.  Endothelium‐Derived Nitric Oxide Synthase Inhibition: Effects on Cerebral Blood Flow, Pial Artery Diameter, and Vascular Morphology in Rats , 1992, Stroke.

[16]  秀樹 森田,et al.  Nitric Oxide(NO)の病態への関与 , 1995 .

[17]  F. Murad,et al.  Regional distribution of EDRF/NO-synthesizing enzyme(s) in rat brain. , 1990, Biochemical and biophysical research communications.

[18]  B. Siesjö,et al.  Cerebral metabolic rate in hypercarbia--a controversy. , 1980, Anesthesiology.

[19]  S. Moncada,et al.  Vascular endothelial cells synthesize nitric oxide from L-arginine , 1988, Nature.

[20]  S. Gardiner,et al.  Regional and cardiac haemodynamic effects of NG‐nitro‐l‐arginine methyl ester in conscious, Long Evans rats , 1990, British journal of pharmacology.

[21]  S. Snyder,et al.  Localization of nitric oxide synthase indicating a neural role for nitric oxide , 1990, Nature.

[22]  E. Nagata,et al.  Inhibition of nitric oxide synthesis induces a significant reduction in local cerebral blood flow in the rat , 1991, Neuroscience Letters.

[23]  A. Gibson,et al.  l‐NG‐nitro arginine (l‐NOARG), a novel, l‐arginine‐reversible inhibitor of endothelium‐dependent vasodilatation in vitro , 1990, British journal of pharmacology.

[24]  S. Shimojyo,et al.  Carbon dioxide and cerebral circulatory control. II. The intravascular effect. , 1967, Archives of neurology.

[25]  O. Inanami,et al.  Nitric oxide (NO) is involved in increased cerebral cortical blood flow following stimulation of the nucleus basalis of Meynert in anesthetized rats , 1992, Neuroscience Letters.

[26]  E. Golanov,et al.  Inhibition of Nitric Oxide Synthesis Increases Focal Ischemic Infarction in Rat , 1992, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[27]  S. Moncada,et al.  Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo , 1990, British journal of pharmacology.

[28]  D. Lodge,et al.  Noncompetitive excitatory amino acid receptor antagonists. , 1990, Trends in pharmacological sciences.

[29]  I L Buxton,et al.  NG-nitro L-arginine methyl ester and other alkyl esters of arginine are muscarinic receptor antagonists. , 1993, Circulation research.

[30]  R. Hemmingsen,et al.  The effect of propranolol on cerebral oxygen consumption and blood flow in the rat: measurements during normocapnia and hypercapnia. , 1979, Acta physiologica Scandinavica.

[31]  E. Kozniewska,et al.  Effects of Endothelium-Derived Nitric Oxide on Cerebral Circulation during Normoxia and Hypoxia in the Rat , 1992, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[32]  S. Shimojyo,et al.  Carbon dioxide and cerebral circulatory control. 3. The effects of brain stem lesions. , 1967, Archives of neurology.

[33]  S. Snyder,et al.  Possible Origins and Distribution of Immunoreactive Nitric Oxide Synthase-Containing Nerve Fibers in Cerebral Arteries , 1993, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[34]  C. Pang,et al.  Pressor effect of NG-nitro-L-arginine in pentobarbital-anesthetized rats. , 1990, Life sciences.

[35]  R. Berne,et al.  Competitive inhibition of nitric oxide synthase prevents the cortical hyperemia associated with peripheral nerve stimulation. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[36]  C Iadecola Does nitric oxide mediate the increases in cerebral blood flow elicited by hypercapnia? , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[37]  S. Moncada,et al.  Nitric oxide: physiology, pathophysiology, and pharmacology. , 1991, Pharmacological reviews.

[38]  D. Heistad,et al.  Factors involved in the physiological regulation of the cerebral circulation. , 1984, Reviews of physiology, biochemistry and pharmacology.

[39]  S Moncada,et al.  Biosynthesis of nitric oxide from L-arginine. A pathway for the regulation of cell function and communication. , 1989, Biochemical pharmacology.

[40]  J. F. Howell,et al.  Pairwise Multiple Comparison Procedures with Unequal N’s and/or Variances: A Monte Carlo Study , 1976 .

[41]  Paul A. Games,et al.  Simultaneous pairwise multiple comparison procedures for means when sample sizes are unequal. , 1981 .

[42]  R. Bryan Cerebral blood flow and energy metabolism during stress. , 1990, The American journal of physiology.

[43]  D. Harrison,et al.  Evidence for an Astrocyte‐Derived Vasorelaxing Factor with Properties Similar to Nitric Oxide , 1990, Journal of neurochemistry.

[44]  Robert E. Anderson,et al.  Effect in cat locus coeruleus lesions on the response of cerebral blood flow and cardiac output to altered paCO2 , 1986, Brain Research.

[45]  R. Karler,et al.  The role of carbon dioxide in the nervous system. , 1960, Anesthesiology.

[46]  B. Siesjö,et al.  Cerebral Blood Flow and Oxygen Consumption in the Rat Brain during Extreme Hypercarbia , 1979, Anesthesiology.

[47]  E. Mackenzie,et al.  Influence of endogenous norepinephrine on cerebral blood flow and metabolism. , 1976, The American journal of physiology.

[48]  L. Ignarro Signal transduction mechanisms involving nitric oxide. , 1991, Biochemical pharmacology.