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Abstract

Biotransformation of glyceryl trinitrate occurs concurrently with relaxation of rabbit aorta.

J F Brien, B E McLaughlin, T H Breedon, B M Bennett, K Nakatsu and G S Marks
Journal of Pharmacology and Experimental Therapeutics May 1986, 237 (2) 608-614;
J F Brien
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B E McLaughlin
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T H Breedon
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B M Bennett
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K Nakatsu
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G S Marks
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Abstract

This study was conducted to test the hypothesis that biotransformation of glyceryl trinitrate (GTN) is involved in GTN-induced relaxation of vascular smooth muscle. Isolated rabbit aortic strips (RAS) were contracted submaximally with phenylephrine (PE) and then were incubated with 0.5 microM [14C]GTN in a time course study. GTN-induced relaxation (inhibition of PE-induced tone) of RAS was monitored and tissue GTN and glyceryl-1,2- and 1,3-dinitrate (GDN) concentrations were measured by thin-layer chromatography and liquid scintillation spectrometry at 0.5, 1, 2 and 20 min after incubation. Biotransformation of GTN to GDN occurred during GTN-induced relaxation of RAS. The tissue GDN concentration was dependent on the time duration of incubation with GTN and was related to the magnitude of GTN-induced tissue relaxation. At the 20-min interval, the GDN concentration in the incubation medium indicated appreciable efflux of GDN metabolites from the RAS. In the biotransformation of GTN by RAS, there was about 4-fold preferential formation of 1,2-GDN compared with 1,3-GDN. RAS were made tolerant to GTN in vitro by incubation with 500 microM GTN for 1 hr. After washing, GTN-tolerant and nontolerant (incubation with vehicle for 1 hr) RAS were contracted submaximally with PE, and then were incubated with 0.5 microM [14C]GTN for 2 min. GTN-induced relaxation of RAS and tissue GDN concentration were significantly less for GTN-tolerant tissue compared with nontolerant tissue. Tissue GTN concentration was similar for both GTN-tolerant and nontolerant RAS, which indicated that the tissue uptake of GTN was similar and that GTN biotransformation was diminished in tolerant tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 237, Issue 2
1 May 1986
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Abstract

Biotransformation of glyceryl trinitrate occurs concurrently with relaxation of rabbit aorta.

J F Brien, B E McLaughlin, T H Breedon, B M Bennett, K Nakatsu and G S Marks
Journal of Pharmacology and Experimental Therapeutics May 1, 1986, 237 (2) 608-614;

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Abstract

Biotransformation of glyceryl trinitrate occurs concurrently with relaxation of rabbit aorta.

J F Brien, B E McLaughlin, T H Breedon, B M Bennett, K Nakatsu and G S Marks
Journal of Pharmacology and Experimental Therapeutics May 1, 1986, 237 (2) 608-614;
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