Nitric-oxide synthase-containing nerves facilitate adrenergic transmitter release in sheep middle cerebral arteries

Emmanuel N. Mbaku, Lubo Zhang, Sue P. Duckles, John Buchholz

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Cerebral blood vessels contain both sympathetic and nitric oxide (NO) synthase (NOS)-containing nerves. NO has been proposed to modulate smooth muscle function and adrenergic nerve activity, and the nature of this modulation is controversial: some data show NO inhibits norepinephrine (NE) release, whereas others suggest that NO augments release. To test the hypothesis that in cerebral arteries NO released by NOS-containing nerves augments stimulation-evoked NE release, we used direct measurement of NE and NO release in isolated sheep middle cerebral arteries. The facial artery, which has not been reported to be innervated with NOS-containing nerves, was used as an artery comparison model. HPLC and redox electrochemical detection was used to measure NE, and NO was measured by chemiluminescence. Stimulation-evoked NE release from the middle cerebral artery significantly declined in the presence of the NOS inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME). The effect of L-NAME was reversed by the addition of the NO donor S-nitroso-N-acetyl-DL-penicillamine. In contrast, in facial arteries, L-NAME had no effect on stimulation-evoked NE release, whereas S-nitroso-N- acetyl-DL-penicillamine still significantly elevated NE release. Activation of perivascular nerves significantly increased NE release in both the middle cerebral and facial arteries. However, when NO was measured in the same samples, stimulation-evoked release of NO was significantly increased compared with basal release only in middle cerebral arteries. These data support the concept that cerebral arteries in the sheep contain both adrenergic and NOS-containing nerves. Furthermore, this study provides succinct evidence that NO released from NOS nerves augments stimulation- evoked NE release.

Original languageEnglish (US)
Pages (from-to)397-402
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume293
Issue number2
StatePublished - May 1 2000

Fingerprint

Middle Cerebral Artery
Nitric Oxide Synthase
Adrenergic Agents
Sheep
Norepinephrine
Nitric Oxide
NG-Nitroarginine Methyl Ester
Penicillamine
Cerebral Arteries
Arteries
Nitric Oxide Donors
Luminescence
Oxidation-Reduction
Smooth Muscle
Blood Vessels
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Nitric-oxide synthase-containing nerves facilitate adrenergic transmitter release in sheep middle cerebral arteries. / Mbaku, Emmanuel N.; Zhang, Lubo; Duckles, Sue P.; Buchholz, John.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 293, No. 2, 01.05.2000, p. 397-402.

Research output: Contribution to journalArticle

Mbaku, Emmanuel N. ; Zhang, Lubo ; Duckles, Sue P. ; Buchholz, John. / Nitric-oxide synthase-containing nerves facilitate adrenergic transmitter release in sheep middle cerebral arteries. In: Journal of Pharmacology and Experimental Therapeutics. 2000 ; Vol. 293, No. 2. pp. 397-402.
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