Selective arterial dilatation by glyceryl trinitrate is not associated with nitric oxide formation in vitro

Mark R. Miller, Stuart Grant, Roger M. Wadsworth

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Glyceryl trinitrate (GTN) is the most commonly used anti-anginal agent, yet its mechanism of action has still to be fully established. Release of nitric oxide (NO) and the selectivity of GTN in the venous system are believed to be crucial to this drug's anti-anginal action. Methods: Rat superior mesenteric arteries and renal veins were mounted in a wire myograph with an intraluminal NO microsensor. Results: In the superior mesenteric arteries, GTN (1 nM to 10 µM) produced a dose-dependent vasodilatation without NO release, except at concentrations supramaximal for relaxation. GTN was found to be markedly less potent in a wide range of veins tested, and lowering the oxygen concentrations in the myograph to that of the venous system did not improve the venodilator activity of GTN. Conclusion: This is the first time that NO release from GTN has been monitored electrochemically in real time, simultaneously with vasodilatation. Unlike the endothelium-dependent vasodilator carbachol, NO could only be measured at concentrations of GTN that are supramaximal for relaxation. GTN was found to be arterioselective in vitro, even when oxygen levels were lowered to mimic those of the venous system in vivo
LanguageEnglish
Pages375-385
Number of pages11
JournalJournal of Vascular Research
Volume45
Issue number5
DOIs
Publication statusPublished - 2008

Fingerprint

Nitroglycerin
Dilatation
Nitric Oxide
Superior Mesenteric Artery
Vasodilation
Oxygen
Mesenteric Veins
Endothelium-Dependent Relaxing Factors
Renal Veins
In Vitro Techniques
Carbachol
Veins
Pharmaceutical Preparations

Keywords

  • glyceryl trinitrate
  • nitric oxide
  • arteries
  • veins
  • coronary disease
  • hypoxia
  • pharmacology

Cite this

Miller, Mark R. ; Grant, Stuart ; Wadsworth, Roger M. / Selective arterial dilatation by glyceryl trinitrate is not associated with nitric oxide formation in vitro. In: Journal of Vascular Research. 2008 ; Vol. 45, No. 5. pp. 375-385.
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abstract = "Glyceryl trinitrate (GTN) is the most commonly used anti-anginal agent, yet its mechanism of action has still to be fully established. Release of nitric oxide (NO) and the selectivity of GTN in the venous system are believed to be crucial to this drug's anti-anginal action. Methods: Rat superior mesenteric arteries and renal veins were mounted in a wire myograph with an intraluminal NO microsensor. Results: In the superior mesenteric arteries, GTN (1 nM to 10 µM) produced a dose-dependent vasodilatation without NO release, except at concentrations supramaximal for relaxation. GTN was found to be markedly less potent in a wide range of veins tested, and lowering the oxygen concentrations in the myograph to that of the venous system did not improve the venodilator activity of GTN. Conclusion: This is the first time that NO release from GTN has been monitored electrochemically in real time, simultaneously with vasodilatation. Unlike the endothelium-dependent vasodilator carbachol, NO could only be measured at concentrations of GTN that are supramaximal for relaxation. GTN was found to be arterioselective in vitro, even when oxygen levels were lowered to mimic those of the venous system in vivo",
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Selective arterial dilatation by glyceryl trinitrate is not associated with nitric oxide formation in vitro. / Miller, Mark R.; Grant, Stuart; Wadsworth, Roger M.

In: Journal of Vascular Research, Vol. 45, No. 5, 2008, p. 375-385.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Selective arterial dilatation by glyceryl trinitrate is not associated with nitric oxide formation in vitro

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AU - Grant, Stuart

AU - Wadsworth, Roger M.

PY - 2008

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N2 - Glyceryl trinitrate (GTN) is the most commonly used anti-anginal agent, yet its mechanism of action has still to be fully established. Release of nitric oxide (NO) and the selectivity of GTN in the venous system are believed to be crucial to this drug's anti-anginal action. Methods: Rat superior mesenteric arteries and renal veins were mounted in a wire myograph with an intraluminal NO microsensor. Results: In the superior mesenteric arteries, GTN (1 nM to 10 µM) produced a dose-dependent vasodilatation without NO release, except at concentrations supramaximal for relaxation. GTN was found to be markedly less potent in a wide range of veins tested, and lowering the oxygen concentrations in the myograph to that of the venous system did not improve the venodilator activity of GTN. Conclusion: This is the first time that NO release from GTN has been monitored electrochemically in real time, simultaneously with vasodilatation. Unlike the endothelium-dependent vasodilator carbachol, NO could only be measured at concentrations of GTN that are supramaximal for relaxation. GTN was found to be arterioselective in vitro, even when oxygen levels were lowered to mimic those of the venous system in vivo

AB - Glyceryl trinitrate (GTN) is the most commonly used anti-anginal agent, yet its mechanism of action has still to be fully established. Release of nitric oxide (NO) and the selectivity of GTN in the venous system are believed to be crucial to this drug's anti-anginal action. Methods: Rat superior mesenteric arteries and renal veins were mounted in a wire myograph with an intraluminal NO microsensor. Results: In the superior mesenteric arteries, GTN (1 nM to 10 µM) produced a dose-dependent vasodilatation without NO release, except at concentrations supramaximal for relaxation. GTN was found to be markedly less potent in a wide range of veins tested, and lowering the oxygen concentrations in the myograph to that of the venous system did not improve the venodilator activity of GTN. Conclusion: This is the first time that NO release from GTN has been monitored electrochemically in real time, simultaneously with vasodilatation. Unlike the endothelium-dependent vasodilator carbachol, NO could only be measured at concentrations of GTN that are supramaximal for relaxation. GTN was found to be arterioselective in vitro, even when oxygen levels were lowered to mimic those of the venous system in vivo

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