The effect of the nitric oxide synthase inhibitor L-NMMA on basal CBF and vasoneuronal coupling in man: a PET study

R P White, C Hindley, P M Bloomfield, V J Cunningham, P Vallance, D J Brooks, H S Markus

Research output: Contribution to journalArticle

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Abstract

Nitric oxide (NO) regulates basal CBF. In a number of animal models NO has been implicated in the mediation of the regional changes in CBF (rCBF) that accompany neuronal activation (vasoneuronal coupling). However, some results in animal models have failed to confirm this finding, and the validity of extrapolation to man from animal data is uncertain. To determine the contribution of NO to basal global CBF and activation-induced changes in rCBF, the authors have performed quantitative H2(15)O positron emission tomography (PET) studies before and after administration of the non-isoform-specific NO synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), in 10 healthy male volunteers. Learning a novel sequence of finger movements was used as a paradigm to induce regional frontal cortex activation. The effect of NO synthase inhibition on the magnitude and pattern of activation was determined. Resting global CBF fell from 33.3 +/- 5.3 mL x 100 g(-1) x min(-1) at rest before L-NMMA, to 26.5 +/- 7.7 mL x 100 g(-1) x min(-1) after L-NMMA (P = 0.001). This fall was reversed by L-arginine administration. Learning sequential finger movements induced increases in rCBF in the left motor, right prefrontal, and bilateral premotor cortices. After NO synthase inhibition with L-NMMA, there was no change in this pattern of activation and no reduction in the magnitude of rCBF responses at the foci of maximal stimulation before and after L-NMMA. These findings confirm that NO production contributes to basal CBF regulation in man, but show that systemic NO synthase inhibition with L-NMMA does not impair regional vasoneuronal coupling.
Original languageEnglish
Pages (from-to)673-8
Number of pages6
JournalJournal of Cerebral Blood Flow and Metabolism
Volume19
Issue number6
DOIs
Publication statusPublished - 1999

Fingerprint

omega-N-Methylarginine
Nitric Oxide Synthase
Positron-Emission Tomography
Nitric Oxide
Fingers
Arginine
Animal Models
Learning
Motor Cortex
Frontal Lobe
Healthy Volunteers
Inhibition (Psychology)

Keywords

  • Adult
  • Blood Pressure
  • Brain
  • Cerebrovascular Circulation
  • Enzyme Inhibitors
  • Humans
  • Male
  • Nitric Oxide Synthase
  • Tomography, Emission-Computed
  • omega-N-Methylarginine

Cite this

The effect of the nitric oxide synthase inhibitor L-NMMA on basal CBF and vasoneuronal coupling in man: a PET study. / White, R P; Hindley, C; Bloomfield, P M; Cunningham, V J; Vallance, P; Brooks, D J; Markus, H S.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 19, No. 6, 1999, p. 673-8.

Research output: Contribution to journalArticle

White, R P ; Hindley, C ; Bloomfield, P M ; Cunningham, V J ; Vallance, P ; Brooks, D J ; Markus, H S. / The effect of the nitric oxide synthase inhibitor L-NMMA on basal CBF and vasoneuronal coupling in man: a PET study. In: Journal of Cerebral Blood Flow and Metabolism. 1999 ; Vol. 19, No. 6. pp. 673-8.
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T1 - The effect of the nitric oxide synthase inhibitor L-NMMA on basal CBF and vasoneuronal coupling in man: a PET study

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AU - Bloomfield, P M

AU - Cunningham, V J

AU - Vallance, P

AU - Brooks, D J

AU - Markus, H S

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N2 - Nitric oxide (NO) regulates basal CBF. In a number of animal models NO has been implicated in the mediation of the regional changes in CBF (rCBF) that accompany neuronal activation (vasoneuronal coupling). However, some results in animal models have failed to confirm this finding, and the validity of extrapolation to man from animal data is uncertain. To determine the contribution of NO to basal global CBF and activation-induced changes in rCBF, the authors have performed quantitative H2(15)O positron emission tomography (PET) studies before and after administration of the non-isoform-specific NO synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), in 10 healthy male volunteers. Learning a novel sequence of finger movements was used as a paradigm to induce regional frontal cortex activation. The effect of NO synthase inhibition on the magnitude and pattern of activation was determined. Resting global CBF fell from 33.3 +/- 5.3 mL x 100 g(-1) x min(-1) at rest before L-NMMA, to 26.5 +/- 7.7 mL x 100 g(-1) x min(-1) after L-NMMA (P = 0.001). This fall was reversed by L-arginine administration. Learning sequential finger movements induced increases in rCBF in the left motor, right prefrontal, and bilateral premotor cortices. After NO synthase inhibition with L-NMMA, there was no change in this pattern of activation and no reduction in the magnitude of rCBF responses at the foci of maximal stimulation before and after L-NMMA. These findings confirm that NO production contributes to basal CBF regulation in man, but show that systemic NO synthase inhibition with L-NMMA does not impair regional vasoneuronal coupling.

AB - Nitric oxide (NO) regulates basal CBF. In a number of animal models NO has been implicated in the mediation of the regional changes in CBF (rCBF) that accompany neuronal activation (vasoneuronal coupling). However, some results in animal models have failed to confirm this finding, and the validity of extrapolation to man from animal data is uncertain. To determine the contribution of NO to basal global CBF and activation-induced changes in rCBF, the authors have performed quantitative H2(15)O positron emission tomography (PET) studies before and after administration of the non-isoform-specific NO synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), in 10 healthy male volunteers. Learning a novel sequence of finger movements was used as a paradigm to induce regional frontal cortex activation. The effect of NO synthase inhibition on the magnitude and pattern of activation was determined. Resting global CBF fell from 33.3 +/- 5.3 mL x 100 g(-1) x min(-1) at rest before L-NMMA, to 26.5 +/- 7.7 mL x 100 g(-1) x min(-1) after L-NMMA (P = 0.001). This fall was reversed by L-arginine administration. Learning sequential finger movements induced increases in rCBF in the left motor, right prefrontal, and bilateral premotor cortices. After NO synthase inhibition with L-NMMA, there was no change in this pattern of activation and no reduction in the magnitude of rCBF responses at the foci of maximal stimulation before and after L-NMMA. These findings confirm that NO production contributes to basal CBF regulation in man, but show that systemic NO synthase inhibition with L-NMMA does not impair regional vasoneuronal coupling.

KW - Adult

KW - Blood Pressure

KW - Brain

KW - Cerebrovascular Circulation

KW - Enzyme Inhibitors

KW - Humans

KW - Male

KW - Nitric Oxide Synthase

KW - Tomography, Emission-Computed

KW - omega-N-Methylarginine

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M3 - Article

VL - 19

SP - 673

EP - 678

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 6

ER -