Selective arterial dilatation by glyceryl trinitrate is not associated with nitric oxide formation in vitro.
OBJECTIVE
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 microM) 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.


CONCLUSIONS
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.
Miller
Mark R
MR
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, UK.
Grant
Stuart
S
Wadsworth
Roger M
RM
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects* / Q000378:metabolism; D009213:Myography; D009569:Nitric Oxide / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012082:Renal Veins / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D002217:Carbachol; D005996:Nitroglycerin; D007545:Isoproterenol; D010100:Oxygen