Nitric oxide mediation of chemoregulation but not autoregulation of cerebral blood flow in primates

Restricted access

✓ The authors sought to develop a model for assessing in vivo regulation of cerebral vasoregulation by nitric oxide (NO), originally described as endothelial-derived relaxing factor, and to use this model to establish the role of NO in the regulation of cerebral blood flow (CBF) in primates. By using regional intraarterial perfusion, the function of NO in cerebral vasoregulation was examined without producing confounding systemic physiological effects. Issues examined were: whether resting vasomotor tone requires NO; whether NO mediates vasodilation during chemoregulation and autoregulation of CBF; and whether there is a relationship between the degree of hypercapnia and hypotension and NO production. Twelve anesthetized (0.5% isoflurane) cynomolgus monkeys were monitored continuously for cortical CBF, PaCO2, and mean arterial pressure (MAP), which were systematically altered to provide control and experimental curves of chemoregulation (CBF vs. PaCO2) and autoregulation (CBF vs. MAP) during continuous intracarotid infusion of 1) saline and 2) an NO synthase inhibitor (NOSI), either l-n-monomethyl arginine or nitro l-arginine.

During basal conditions (PaCO2 of 38–42 mm Hg) NOSI infusion of internal carotid artery (ICA) reduced cortical CBF from 62 (saline) to 53 ml/100 g/per minute (p < 0.01), although there was no effect on MAP. Increased CBF in response to hypercapnia was completely blocked by ICA NOSI. The difference in regional (r)CBF between ICA saline and NOSI infusion increased linearly with PaCO2 when PaCO2 was greater than 40 mm Hg, indicating a graded relationship of NO production, increasing PaCO2, and increasing CBF. Diminution of CBF with NOSI infusion was reversed by simultaneous ICA infusion of l-arginine, indicating a direct role of NO synthesis in the chemoregulation of CBF.

Hypotension and hypertension were induced with trimethaphan camsylate (Arfonad) and phenylephrine at constant PaCO2 (40 ± 1 mm Hg). Autoregulation in response to changes in MAP from 50 to 140 mm Hg was unaffected by ICA infusion of NOSI.

In primates, cerebral vascular tone is modulated in vivo by NO; continuous release of NO is necessary to maintain homeostatic cerebral vasodilation; vasodilation during chemoregulation of CBF is mediated directly by NO production; autoregulatory vasodilation with hypotension is not mediated by NO; and increasing PaCO2 induces increased NO production.

Article Information

Contributor Notes

Address for Dr. Thompson: University of Utah School of Medicine, Salt Lake City, Utah.Address reprint requests to: Edward H. Oldfield, M.D., Building 10, Room 5D-37, National Institutes of Health, Bethesda, Maryland 20892.

© AANS, except where prohibited by US copyright law.

Headings
References
  • 1.

    Afshar JKBPluta RMBoock RJet al: Effect of intracarotid nitric oxide on primate cerebral vasospasm after subarachnoid hemorrhage. J Neurosurg 83:1181221995Afshar JKB Pluta RM Boock RJ et al: Effect of intracarotid nitric oxide on primate cerebral vasospasm after subarachnoid hemorrhage. J Neurosurg 83:118–122 1995

    • Search Google Scholar
    • Export Citation
  • 2.

    Bredt DSHwang PMSnyder SH: Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature 347:7687701990Bredt DS Hwang PM Snyder SH: Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature 347:768–770 1990

    • Search Google Scholar
    • Export Citation
  • 3.

    Brian JE JrKennedy RH: Modulation of cerebral arterial tone by endothelium-derived relaxing factor. Am J Physiol 264:H1245H12501993Brian JE Jr Kennedy RH: Modulation of cerebral arterial tone by endothelium-derived relaxing factor. Am J Physiol 264:H1245–H1250 1993

    • Search Google Scholar
    • Export Citation
  • 4.

    Buchanan JEPhillis JW: The role of nitric oxide in the regulation of cerebral blood flow. Brain Res 610:2482551993Buchanan JE Phillis JW: The role of nitric oxide in the regulation of cerebral blood flow. Brain Res 610:248–255 1993

    • Search Google Scholar
    • Export Citation
  • 5.

    Carter LPErspamer RBro WJ: Cerebral blood flow: thermal diffusion vs. isotope clearance. Stroke 12:5135181981Carter LP Erspamer R Bro WJ: Cerebral blood flow: thermal diffusion vs. isotope clearance. Stroke 12:513–518 1981

    • Search Google Scholar
    • Export Citation
  • 6.

    Craven PADeRubertis FR: Restoration of the responsiveness of purified guanylate cyclase to nitrosoguanidine, nitric oxide, and related activators by heme and hemeproteins. Evidence for involvement of the paramagnetic nitrosyl-heme complex in enzyme activation. J Biol Chem 253:843384431978Craven PA DeRubertis FR: Restoration of the responsiveness of purified guanylate cyclase to nitrosoguanidine nitric oxide and related activators by heme and hemeproteins. Evidence for involvement of the paramagnetic nitrosyl-heme complex in enzyme activation. J Biol Chem 253:8433–8443 1978

    • Search Google Scholar
    • Export Citation
  • 7.

    De Sousa Pereira JMM: Histological, histochemical and microsurgical research on anatomophysiological basis of neurogenic control of cerebral blood flow. Acta Neurol Scand Suppl 72:94951979De Sousa Pereira JMM: Histological histochemical and microsurgical research on anatomophysiological basis of neurogenic control of cerebral blood flow. Acta Neurol Scand Suppl 72:94–95 1979

    • Search Google Scholar
    • Export Citation
  • 8.

    Faleiro LCMMachado CRSGripp A Jret al: Cerebral vasospasm: presence of mast cells in human cerebral arteries after aneurysm rupture. Preliminary report. J Neurosurg 54:7337351981Faleiro LCM Machado CRS Gripp A Jr et al: Cerebral vasospasm: presence of mast cells in human cerebral arteries after aneurysm rupture. Preliminary report. J Neurosurg 54:733–735 1981

    • Search Google Scholar
    • Export Citation
  • 9.

    Faraci FM: Role of endothelium-derived relaxing factor in cerebral circulation: large arteries vs. microcirculation. Am J Physiol 261:H1038H10421991Faraci FM: Role of endothelium-derived relaxing factor in cerebral circulation: large arteries vs. microcirculation. Am J Physiol 261:H1038–H1042 1991

    • Search Google Scholar
    • Export Citation
  • 10.

    Faraci FM: Role of nitric oxide in regulation of basilar artery tone in vivo. Am J Physiol 259:H1216H12211990Faraci FM: Role of nitric oxide in regulation of basilar artery tone in vivo. Am J Physiol 259:H1216–H1221 1990

    • Search Google Scholar
    • Export Citation
  • 11.

    Feelisch Mte Poel MZamora Ret al: Understanding the controversy over the identity of EDRF. Nature 368:62651994Feelisch M te Poel M Zamora R et al: Understanding the controversy over the identity of EDRF. Nature 368:62–65 1994

    • Search Google Scholar
    • Export Citation
  • 12.

    Fischer-Nakielski HSchrör K: Nitric oxide is the endothelium-derived relaxing factor in bovine pial arterioles. Stroke 21 (Suppl IV):IV–46IV–481990Fischer-Nakielski H Schrör K: Nitric oxide is the endothelium-derived relaxing factor in bovine pial arterioles. Stroke 21 (Suppl IV):IV–46–IV–48 1990

    • Search Google Scholar
    • Export Citation
  • 13.

    Fisher CMKistler JPDavis JM: Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computed tomography scanning. Neurosurgery 6:191980Fisher CM Kistler JP Davis JM: Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computed tomography scanning. Neurosurgery 6:1–9 1980

    • Search Google Scholar
    • Export Citation
  • 14.

    Fog M: Cerebral circulation. The reaction of the pial arteries to a fall in blood pressure. Arch Neurol Psychiatry 37:3513641937Fog M: Cerebral circulation. The reaction of the pial arteries to a fall in blood pressure. Arch Neurol Psychiatry 37:351–364 1937

    • Search Google Scholar
    • Export Citation
  • 15.

    Fog M: Cerebral circulation. II. Reaction of pial arteries to increase in blood pressure. Arch Neurol Psychiatry 41:2602681937Fog M: Cerebral circulation. II. Reaction of pial arteries to increase in blood pressure. Arch Neurol Psychiatry 41:260–268 1937

    • Search Google Scholar
    • Export Citation
  • 16.

    Frazee JGiannotta SLStern WE: Intravenous nitroglycerin for the treatment of chronic cerebral vasoconstriction in the primate. J Neurosurg 55:8658681981Frazee J Giannotta SL Stern WE: Intravenous nitroglycerin for the treatment of chronic cerebral vasoconstriction in the primate. J Neurosurg 55:865–868 1981

    • Search Google Scholar
    • Export Citation
  • 17.

    Fujiwara SKassell NFSasaki Tet al: Selective hemoglobin inhibition of endothelium-dependent vasodilation of rabbit basilar artery. J Neurosurg 64:4454521986Fujiwara S Kassell NF Sasaki T et al: Selective hemoglobin inhibition of endothelium-dependent vasodilation of rabbit basilar artery. J Neurosurg 64:445–452 1986

    • Search Google Scholar
    • Export Citation
  • 18.

    Furchgott RFZawadzki JV: The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:3733761980Furchgott RF Zawadzki JV: The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376 1980

    • Search Google Scholar
    • Export Citation
  • 19.

    Gaines CCarter LPCrowell RM: Comparison of local cerebral blood flow determined by thermal and hydrogen clearance. Stroke 14:66691983Gaines C Carter LP Crowell RM: Comparison of local cerebral blood flow determined by thermal and hydrogen clearance. Stroke 14:66–69 1983

    • Search Google Scholar
    • Export Citation
  • 20.

    Goadsby PJKaube HHoskin KL: Nitric oxide synthesis couples cerebral blood flow and metabolism. Brain Res 595:1671701992Goadsby PJ Kaube H Hoskin KL: Nitric oxide synthesis couples cerebral blood flow and metabolism. Brain Res 595:167–170 1992

    • Search Google Scholar
    • Export Citation
  • 21.

    Gonzalez CEstrada C: Nitric oxide mediates the neurogenic vasodilation of bovine cerebral arteries. J Cereb Blood Flow Metab 11:3663701991Gonzalez C Estrada C: Nitric oxide mediates the neurogenic vasodilation of bovine cerebral arteries. J Cereb Blood Flow Metab 11:366–370 1991

    • Search Google Scholar
    • Export Citation
  • 22.

    Heinzel BJohn MKlatt Pet al: Ca2+/calmodulin-dependent formation of hydrogen peroxide by brain nitric oxide synthase. Biochem J 281:6276301992Heinzel B John M Klatt P et al: Ca2+/calmodulin-dependent formation of hydrogen peroxide by brain nitric oxide synthase. Biochem J 281:627–630 1992

    • Search Google Scholar
    • Export Citation
  • 23.

    Heros RCZervas NTLavyne MHet al: Reversal of experimental cerebral vasospasm by intravenous nitroprusside therapy. Surg Neurol 6:2272291976Heros RC Zervas NT Lavyne MH et al: Reversal of experimental cerebral vasospasm by intravenous nitroprusside therapy. Surg Neurol 6:227–229 1976

    • Search Google Scholar
    • Export Citation
  • 24.

    Iadecola C: Does nitric oxide mediate the increases in cerebral blood flow elicited by hypercapnia? Proc Natl Acad Sci USA 89:391339161992Iadecola C: Does nitric oxide mediate the increases in cerebral blood flow elicited by hypercapnia? Proc Natl Acad Sci USA 89:3913–3916 1992

    • Search Google Scholar
    • Export Citation
  • 25.

    Iadecola CBeitz ARenno Wet al: Nitric oxide synthase-containing neural processes on large cerebral arteries and cerebral microvessels. Brain Res 606:1481551993Iadecola C Beitz A Renno W et al: Nitric oxide synthase-containing neural processes on large cerebral arteries and cerebral microvessels. Brain Res 606:148–155 1993

    • Search Google Scholar
    • Export Citation
  • 26.

    Iadecola CPelligrino DAMoskowitz MAet al: Nitric oxide synthase inhibition and cerebrovascular regulation. J Cereb Blood Flow Metab 14:1751921994Iadecola C Pelligrino DA Moskowitz MA et al: Nitric oxide synthase inhibition and cerebrovascular regulation. J Cereb Blood Flow Metab 14:175–192 1994

    • Search Google Scholar
    • Export Citation
  • 27.

    Iadecola CXu X: Nitro-L-arginine attenuates hypercapnic cerebrovasodilation without affecting cerebral metabolism. Am J Physiol 6:R518R5251994Iadecola C Xu X: Nitro-L-arginine attenuates hypercapnic cerebrovasodilation without affecting cerebral metabolism. Am J Physiol 6:R518–R525 1994

    • Search Google Scholar
    • Export Citation
  • 28.

    Iadecola CZhang F: Nitric oxide-dependent and -independent components of cerebrovasodilation elicited by hypercapnia. Am J Physiol 266:R546R5521994Iadecola C Zhang F: Nitric oxide-dependent and -independent components of cerebrovasodilation elicited by hypercapnia. Am J Physiol 266:R546–R552 1994

    • Search Google Scholar
    • Export Citation
  • 29.

    Iadecola CZhang FXu X: Role of nitric oxide synthase-containing vascular nerves in cerebrovasodilation elicited from cerebellum. Am J Physiol 264:R738R7461993Iadecola C Zhang F Xu X: Role of nitric oxide synthase-containing vascular nerves in cerebrovasodilation elicited from cerebellum. Am J Physiol 264:R738–R746 1993

    • Search Google Scholar
    • Export Citation
  • 30.

    Ignarro LJ: Nitric oxide. A novel signal transduction mechanism for transcellular communication. Hypertension 16:4774831990Ignarro LJ: Nitric oxide. A novel signal transduction mechanism for transcellular communication. Hypertension 16:477–483 1990

    • Search Google Scholar
    • Export Citation
  • 31.

    Ignarro LJByrns REBuga GMet al: Endothelium-derived relaxing factor from pulmonary artery and vein possesses pharmacologic and chemical properties identical to those of the nitric oxide radical. Circ Res 61:8668791987Ignarro LJ Byrns RE Buga GM et al: Endothelium-derived relaxing factor from pulmonary artery and vein possesses pharmacologic and chemical properties identical to those of the nitric oxide radical. Circ Res 61:866–879 1987

    • Search Google Scholar
    • Export Citation
  • 32.

    Ignarro LJDegnan JNBaricos WHet al: Activation of purified guanylate cyclase by nitric oxide requires heme. Comparison of heme-deficient, heme-reconstituted, and heme-containing forms of soluble enzyme from bovine lung. Biochim Biophys Acta 718:49591982Ignarro LJ Degnan JN Baricos WH et al: Activation of purified guanylate cyclase by nitric oxide requires heme. Comparison of heme-deficient heme-reconstituted and heme-containing forms of soluble enzyme from bovine lung. Biochim Biophys Acta 718:49–59 1982

    • Search Google Scholar
    • Export Citation
  • 33.

    Kanamaru KWaga SKojima Tet al: Endothelium-dependent relaxation of canine basilar arteries. Part 2. Inhibition by hemoglobin and and cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhage. Stroke 18:9389431987Kanamaru K Waga S Kojima T et al: Endothelium-dependent relaxation of canine basilar arteries. Part 2. Inhibition by hemoglobin and and cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhage. Stroke 18:938–943 1987

    • Search Google Scholar
    • Export Citation
  • 34.

    Katsuki SArnold WMittal Cet al: Stimulation of guanylate cyclase by sodium nitroprusside, nitroglycerin, and nitric oxide in various tissue preparations and comparison to the effects of sodium azide and hydroxylamine. J Cyclic Nucleotide Res 3:23351977Katsuki S Arnold W Mittal C et al: Stimulation of guanylate cyclase by sodium nitroprusside nitroglycerin and nitric oxide in various tissue preparations and comparison to the effects of sodium azide and hydroxylamine. J Cyclic Nucleotide Res 3:23–35 1977

    • Search Google Scholar
    • Export Citation
  • 35.

    Kety SSSchmidt CF: The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. J Clin Invest 27:4844921948Kety SS Schmidt CF: The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. J Clin Invest 27:484–492 1948

    • Search Google Scholar
    • Export Citation
  • 36.

    Kety SSSchmidt CF: The nitrous oxide method for the quantitative determination of cerebral blood flow in man; theory, procedure, and normal values. J Clin Invest 27:4764831948Kety SS Schmidt CF: The nitrous oxide method for the quantitative determination of cerebral blood flow in man; theory procedure and normal values. J Clin Invest 27:476–483 1948

    • Search Google Scholar
    • Export Citation
  • 37.

    Khan MFurchgott R: Similarities of behavior of nitric oxide (NO) and endothelium-derived relaxing factor in a perfusion cascade bioassay system. Fed Proc 46:3851987 (Abstract)Khan M Furchgott R: Similarities of behavior of nitric oxide (NO) and endothelium-derived relaxing factor in a perfusion cascade bioassay system. Fed Proc 46:385 1987 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 38.

    Kontos HAWei EPNavari RMet al: Responses of cerebral arteries and arterioles to acute hypotension and hypertension. Am J Physiol 234:H371H3831978Kontos HA Wei EP Navari RM et al: Responses of cerebral arteries and arterioles to acute hypotension and hypertension. Am J Physiol 234:H371–H383 1978

    • Search Google Scholar
    • Export Citation
  • 39.

    Kovách AGSzabó CBenyó Zet al: Effects of NG-nitro-L-arginine and L-arginine on regional blood flow in the cat. J Physiol (London) 449:1831961992Kovách AG Szabó C Benyó Z et al: Effects of NG-nitro-L-arginine and L-arginine on regional blood flow in the cat. J Physiol (London) 449:183–196 1992

    • Search Google Scholar
    • Export Citation
  • 40.

    Koźniewska EOsȩka MStysś T: Effects of endothelium-derived nitric oxide on cerebral circulation during normoxia and hypoxia in the rat. J Cereb Blood Flow Metab 12:3113171992Koźniewska E Osȩka M Stysś T: Effects of endothelium-derived nitric oxide on cerebral circulation during normoxia and hypoxia in the rat. J Cereb Blood Flow Metab 12:311–317 1992

    • Search Google Scholar
    • Export Citation
  • 41.

    Lassen NA: Cerebral blood flow and oxygen consumption in man. Physiol Rev 39:1831891959Lassen NA: Cerebral blood flow and oxygen consumption in man. Physiol Rev 39:183–189 1959

    • Search Google Scholar
    • Export Citation
  • 42.

    Lassen NA: Control of cerebral circulation in health and disease. Circ Res 34:7497601974Lassen NA: Control of cerebral circulation in health and disease. Circ Res 34:749–760 1974

    • Search Google Scholar
    • Export Citation
  • 43.

    Macrae IMDawson DANorrie JDet al: Inhibition of nitric oxide synthesis: effects on cerebral blood flow and glucose utilisation in the rat. J Cereb Blood Flow Metab 13:9859921993Macrae IM Dawson DA Norrie JD et al: Inhibition of nitric oxide synthesis: effects on cerebral blood flow and glucose utilisation in the rat. J Cereb Blood Flow Metab 13:985–992 1993

    • Search Google Scholar
    • Export Citation
  • 44.

    Murphy SMinor RL JrWelk Get al: Evidence for an astrocyte-derived vasorelaxing factor with properties similar to nitric oxide. J Neurochem 55:3493511990Murphy S Minor RL Jr Welk G et al: Evidence for an astrocyte-derived vasorelaxing factor with properties similar to nitric oxide. J Neurochem 55:349–351 1990

    • Search Google Scholar
    • Export Citation
  • 45.

    Niwa KLindauer UVillringer Aet al: Blockade of nitric oxide synthesis in rats strongly attenuates the CBF response to extracellular acidosis. J Cereb Blood Flow Metab 13:5355391993Niwa K Lindauer U Villringer A et al: Blockade of nitric oxide synthesis in rats strongly attenuates the CBF response to extracellular acidosis. J Cereb Blood Flow Metab 13:535–539 1993

    • Search Google Scholar
    • Export Citation
  • 46.

    Nozaki KMoskowitz MAMaynard KIet al: Origins and distribution of nitric oxide synthase-immunoreactive nerve fibers in rat cerebral arteries. Stroke 23:1541993 (Abstract)Nozaki K Moskowitz MA Maynard KI et al: Origins and distribution of nitric oxide synthase-immunoreactive nerve fibers in rat cerebral arteries. Stroke 23:154 1993 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 47.

    Ohta FKobayashi YShinozuka Ket al: Effects of nitro-L-arginine on endothelium-dependent relaxation of canine cerebral arteries. Clin Exp Pharmacol Physiol 13:2852901993Ohta F Kobayashi Y Shinozuka K et al: Effects of nitro-L-arginine on endothelium-dependent relaxation of canine cerebral arteries. Clin Exp Pharmacol Physiol 13:285–290 1993

    • Search Google Scholar
    • Export Citation
  • 48.

    Palmer RMJAshton DSMoncada S: Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333:6646661988 (Letter)Palmer RMJ Ashton DS Moncada S: Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333:664–666 1988 (Letter)

    • Search Google Scholar
    • Export Citation
  • 49.

    Palmer RMJFerrige AGMoncada S: Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:5245261987 (Letter)Palmer RMJ Ferrige AG Moncada S: Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526 1987 (Letter)

    • Search Google Scholar
    • Export Citation
  • 50.

    Panza JAQuyyumi AABrush JE Jret al: Abnormal endothelium-dependent vascular relaxation in patients with essential lypertension. N Engl J Med 323:22271990Panza JA Quyyumi AA Brush JE Jr et al: Abnormal endothelium-dependent vascular relaxation in patients with essential lypertension. N Engl J Med 323:22–27 1990

    • Search Google Scholar
    • Export Citation
  • 51.

    Pelligrino DAKoenig HMAlbrecht RF: Nitric oxide synthesis and and regional cerebral blood flow responses to hypercapnia and hypoxia in the rat. J Cereb Blood Flow Metab 13:80871993Pelligrino DA Koenig HM Albrecht RF: Nitric oxide synthesis and and regional cerebral blood flow responses to hypercapnia and hypoxia in the rat. J Cereb Blood Flow Metab 13:80–87 1993

    • Search Google Scholar
    • Export Citation
  • 52.

    Rosenblum WINishimura HNelson GH: Endothelium-dependent L-Arg- and L-NMMA-sensitive mechanisms regulate tone of brain microvessels. Am J Physiol 259:H1396H14011990Rosenblum WI Nishimura H Nelson GH: Endothelium-dependent L-Arg- and L-NMMA-sensitive mechanisms regulate tone of brain microvessels. Am J Physiol 259:H1396–H1401 1990

    • Search Google Scholar
    • Export Citation
  • 53.

    Sandor PKomjati KReivich Met al: Major role of nitric oxide in the mediation of regional CO2 responsiveness of the cerebral and spinal cord vessels of the cat. J Cereb Blood Flow Metab 14:49581994Sandor P Komjati K Reivich M et al: Major role of nitric oxide in the mediation of regional CO2 responsiveness of the cerebral and spinal cord vessels of the cat. J Cereb Blood Flow Metab 14:49–58 1994

    • Search Google Scholar
    • Export Citation
  • 54.

    Shapiro WWasserman AJPatterson JL: Mechanism and pattern of human cerebrovascular regulation after rapid changes in blood CO2 tension. J Clin Invest 45:9131966Shapiro W Wasserman AJ Patterson JL: Mechanism and pattern of human cerebrovascular regulation after rapid changes in blood CO2 tension. J Clin Invest 45:913 1966

    • Search Google Scholar
    • Export Citation
  • 55.

    Strandgaard SJones JVMackenzie ETet al: Upper limit of cerebral blood flow autoregulation in experimental renovascular hypertension in the baboon. Circ Res 37:1641671975Strandgaard S Jones JV Mackenzie ET et al: Upper limit of cerebral blood flow autoregulation in experimental renovascular hypertension in the baboon. Circ Res 37:164–167 1975

    • Search Google Scholar
    • Export Citation
  • 56.

    Tanaka KFukuuchi YGomi Set al: Inhibition of nitric oxide synthase impairs autoregulation of local cerebral blood flow in the rat. Neuroreport 4:2672701993Tanaka K Fukuuchi Y Gomi S et al: Inhibition of nitric oxide synthase impairs autoregulation of local cerebral blood flow in the rat. Neuroreport 4:267–270 1993

    • Search Google Scholar
    • Export Citation
  • 57.

    Thompson BGPluta RMGirton Met al: Nitric oxide mediates chemoregulation of CBF in primates B. Stroke 23:1541992 (Abstract)Thompson BG Pluta RM Girton M et al: Nitric oxide mediates chemoregulation of CBF in primates B. Stroke 23:154 1992 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 58.

    Vallance PCollier JMoncada S: Effects of endotheliumderived nitric oxide on peripheral arteriolar tone in man. Lancet 2:99710001989Vallance P Collier J Moncada S: Effects of endotheliumderived nitric oxide on peripheral arteriolar tone in man. Lancet 2:997–1000 1989

    • Search Google Scholar
    • Export Citation
  • 59.

    Vane JRÄnggård EEBotting RM: Regulatory functions of the vascular endothelium. N Engl J Med 323:27361990Vane JR Änggård EE Botting RM: Regulatory functions of the vascular endothelium. N Engl J Med 323:27–36 1990

    • Search Google Scholar
    • Export Citation
  • 60.

    Vinall PSimeone F: In vitro myogenic autoregulation in cerebral blood vessels in Heistad DMarcus M (eds): Cerebral Blood Flow: Effects of Nerves and Neurotransmitters. Amsterdam: Elsevier North Holland1982 pp 5764Vinall P Simeone F: In vitro myogenic autoregulation in cerebral blood vessels in Heistad D Marcus M (eds): Cerebral Blood Flow: Effects of Nerves and Neurotransmitters. Amsterdam: Elsevier North Holland 1982 pp 57–64

    • Search Google Scholar
    • Export Citation
  • 61.

    Wang QPaulson OBLassen NA: Effect of nitric oxide blockade by N-nitro-L-arginine on cerebral blood flow response to changes in carbon dioxide tension. J Cereb Blood Flow Metab 12:9479531992Wang Q Paulson OB Lassen NA: Effect of nitric oxide blockade by N-nitro-L-arginine on cerebral blood flow response to changes in carbon dioxide tension. J Cereb Blood Flow Metab 12:947–953 1992

    • Search Google Scholar
    • Export Citation
  • 62.

    Wang QPaulson OBLassen NA: Is autoregulation of cerebral blood flow in rats influenced by nitro-L-arginine, a blocker of the synthesis of nitric oxide? Acta Physiol Scand 145:2972981992Wang Q Paulson OB Lassen NA: Is autoregulation of cerebral blood flow in rats influenced by nitro-L-arginine a blocker of the synthesis of nitric oxide? Acta Physiol Scand 145:297–298 1992

    • Search Google Scholar
    • Export Citation
TrendMD
Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 108 107 3
Full Text Views 167 124 0
PDF Downloads 90 46 0
EPUB Downloads 0 0 0
PubMed
Google Scholar