Activation of Soluble Guanylyl Cyclase by a Factor Other Than Nitric Oxide or Carbon Monoxide Contributes to the Vascular Hyporeactivity to Vasoconstrictor Agents in the Aorta of Rats Treated with Endotoxin

C. C. Wu, Csaba Szabo, S. J. Chen, C. Thiemermann, J. R. Vane

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Abstract

We have examined the role of soluble guanylyl cyclase and possible mediators of its activation in the vascular hyporeactivity caused by bacterial endotoxin (lipopolysaccharide, LPS) ex vivo. Treatment of rats with E. coli LPS (10 mg/kg, i.v. for 3h) resulted in a significant reduction in the contractions elicited by norepinephrine (NE; 10-9-10-6 M) in endothelium-denuded aortic rings ex vivo. Methylene blue or LY-83583, inhibitors of soluble guanylyl cyclase, completely restored contractions to NE, whereas the nitric oxide synthase (NOS) inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME), caused only a partial restoration. Zinc protoporphyrin-IX, an inhibitor of heme oxygenase, did not enhance NE-induced contraction in rings from LPS-treated rats,indicating that the production of carbon monoxide (CO) does not contribute to this vascular hyporeactivity. Indomethacin, an inhibitor of cyclooxygenase, further suppressed the contractions in rings from LPS-treated rats. These results suggest that hyporesponsiveness to NE caused by LPS is due to the activation of soluble guanylyl cyclase, which is partially mediated by NO, but not by CO, Moreover, LPS may induce the production of another mediator(s) that activate soluble guanyyl cyclase in the vascular smooth muscle.

Original languageEnglish (US)
Pages (from-to)436-442
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume201
Issue number1
DOIs
StatePublished - May 30 1994
Externally publishedYes

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Guanylate Cyclase
Vasoconstrictor Agents
Carbon Monoxide
Endotoxins
Blood Vessels
Lipopolysaccharides
Aorta
Rats
Nitric Oxide
Chemical activation
6-anilino-5,8-quinolinedione
Heme Oxygenase (Decyclizing)
Arginine
Cyclooxygenase Inhibitors
Methylene Blue
NG-Nitroarginine Methyl Ester
Vascular Smooth Muscle
Nitric Oxide Synthase
Indomethacin
Escherichia coli

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Biochemistry

Cite this

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title = "Activation of Soluble Guanylyl Cyclase by a Factor Other Than Nitric Oxide or Carbon Monoxide Contributes to the Vascular Hyporeactivity to Vasoconstrictor Agents in the Aorta of Rats Treated with Endotoxin",
abstract = "We have examined the role of soluble guanylyl cyclase and possible mediators of its activation in the vascular hyporeactivity caused by bacterial endotoxin (lipopolysaccharide, LPS) ex vivo. Treatment of rats with E. coli LPS (10 mg/kg, i.v. for 3h) resulted in a significant reduction in the contractions elicited by norepinephrine (NE; 10-9-10-6 M) in endothelium-denuded aortic rings ex vivo. Methylene blue or LY-83583, inhibitors of soluble guanylyl cyclase, completely restored contractions to NE, whereas the nitric oxide synthase (NOS) inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME), caused only a partial restoration. Zinc protoporphyrin-IX, an inhibitor of heme oxygenase, did not enhance NE-induced contraction in rings from LPS-treated rats,indicating that the production of carbon monoxide (CO) does not contribute to this vascular hyporeactivity. Indomethacin, an inhibitor of cyclooxygenase, further suppressed the contractions in rings from LPS-treated rats. These results suggest that hyporesponsiveness to NE caused by LPS is due to the activation of soluble guanylyl cyclase, which is partially mediated by NO, but not by CO, Moreover, LPS may induce the production of another mediator(s) that activate soluble guanyyl cyclase in the vascular smooth muscle.",
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AU - Szabo, Csaba

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AU - Thiemermann, C.

AU - Vane, J. R.

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