Endothelium-independent contractions to N(G)-monomethyl-L-arginine in canine basilar artery

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background and Purpose: N(G)-substituted analogues of L-arginine are potent and selective inhibitors of nitric oxide synthase(s). The present study was designed to determine the effects of these analogues on the vascular smooth muscle of isolated canine basilar arteries. Methods: Basilar artery rings without endothelium were suspended for isometric tension recording in Krebs-Ringer bicarbonate solution bubbled with 94% O2-6% CO2 (temperature=37°C, pH=7.4). A radioimmunoassay technique was used to determine the levels of guanosine 3',5'-cyclic monophosphate (cyclic GMP). Results: N(G)-Monomethyl-L-arginine (L-NMMA) caused concentration-dependent contractions, whereas the D-enantiomer and N(G)-nitro-L-arginine did not. Contractions to L-NMMA were reduced in the presence of L-arginine but not in the presence of D-arginine. Superoxide anions generated by xanthine plus xanthine oxidase in the presence of catalase abolished contractions to L-NMMA but did not affect contractions to the prostaglandin H2/thromboxane A2 agonist U46619. Zaprinast, a selective cyclic GMP phosphodiesterase inhibitor, caused concentration-dependent relaxations. L-NMMA selectively inhibited these relaxations. The inhibitory effect of L-NMMA was reversed in the presence of L-arginine. L-NMMA selectively reduced the basal production of cyclic GMP. Conclusions: These studies suggest that in cerebral arteries, contractions of smooth muscle cells to L-NMMA are mediated by inhibition of nitric oxide synthase with a resultant decrease in the basal production of nitric oxide.

Original languageEnglish (US)
Pages (from-to)1399-1404
Number of pages6
JournalStroke
Volume22
Issue number11
StatePublished - 1991

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omega-N-Methylarginine
Basilar Artery
Endothelium
Arginine
Canidae
Cyclic GMP
Nitric Oxide Synthase
Prostaglandin H2
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Thromboxane A2
Xanthine
Cerebral Arteries
Phosphodiesterase Inhibitors
Xanthine Oxidase
Bicarbonates
Vascular Smooth Muscle
Superoxides
Catalase
Smooth Muscle Myocytes
Radioimmunoassay

Keywords

  • basilar artery
  • dogs
  • endothelium-derived relaxing factor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Endothelium-independent contractions to N(G)-monomethyl-L-arginine in canine basilar artery. / Katusic, Zvonimir S.

In: Stroke, Vol. 22, No. 11, 1991, p. 1399-1404.

Research output: Contribution to journalArticle

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abstract = "Background and Purpose: N(G)-substituted analogues of L-arginine are potent and selective inhibitors of nitric oxide synthase(s). The present study was designed to determine the effects of these analogues on the vascular smooth muscle of isolated canine basilar arteries. Methods: Basilar artery rings without endothelium were suspended for isometric tension recording in Krebs-Ringer bicarbonate solution bubbled with 94{\%} O2-6{\%} CO2 (temperature=37°C, pH=7.4). A radioimmunoassay technique was used to determine the levels of guanosine 3',5'-cyclic monophosphate (cyclic GMP). Results: N(G)-Monomethyl-L-arginine (L-NMMA) caused concentration-dependent contractions, whereas the D-enantiomer and N(G)-nitro-L-arginine did not. Contractions to L-NMMA were reduced in the presence of L-arginine but not in the presence of D-arginine. Superoxide anions generated by xanthine plus xanthine oxidase in the presence of catalase abolished contractions to L-NMMA but did not affect contractions to the prostaglandin H2/thromboxane A2 agonist U46619. Zaprinast, a selective cyclic GMP phosphodiesterase inhibitor, caused concentration-dependent relaxations. L-NMMA selectively inhibited these relaxations. The inhibitory effect of L-NMMA was reversed in the presence of L-arginine. L-NMMA selectively reduced the basal production of cyclic GMP. Conclusions: These studies suggest that in cerebral arteries, contractions of smooth muscle cells to L-NMMA are mediated by inhibition of nitric oxide synthase with a resultant decrease in the basal production of nitric oxide.",
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AB - Background and Purpose: N(G)-substituted analogues of L-arginine are potent and selective inhibitors of nitric oxide synthase(s). The present study was designed to determine the effects of these analogues on the vascular smooth muscle of isolated canine basilar arteries. Methods: Basilar artery rings without endothelium were suspended for isometric tension recording in Krebs-Ringer bicarbonate solution bubbled with 94% O2-6% CO2 (temperature=37°C, pH=7.4). A radioimmunoassay technique was used to determine the levels of guanosine 3',5'-cyclic monophosphate (cyclic GMP). Results: N(G)-Monomethyl-L-arginine (L-NMMA) caused concentration-dependent contractions, whereas the D-enantiomer and N(G)-nitro-L-arginine did not. Contractions to L-NMMA were reduced in the presence of L-arginine but not in the presence of D-arginine. Superoxide anions generated by xanthine plus xanthine oxidase in the presence of catalase abolished contractions to L-NMMA but did not affect contractions to the prostaglandin H2/thromboxane A2 agonist U46619. Zaprinast, a selective cyclic GMP phosphodiesterase inhibitor, caused concentration-dependent relaxations. L-NMMA selectively inhibited these relaxations. The inhibitory effect of L-NMMA was reversed in the presence of L-arginine. L-NMMA selectively reduced the basal production of cyclic GMP. Conclusions: These studies suggest that in cerebral arteries, contractions of smooth muscle cells to L-NMMA are mediated by inhibition of nitric oxide synthase with a resultant decrease in the basal production of nitric oxide.

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