Biotransformation of glyceryl trinitrate occurs concurrently with relaxation of rabbit aorta

Journal Article · Thu May 01 00:00:00 EDT 1986 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:5654218

Brien, J F; McLaughlin, B E; Breedon, T H; Bennett, B M; Nakatsu, K; Marks, G S

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 (/sup 14/C)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 (/sup 14/C)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.(ABST

• Research Organization: Queen's Univ., Kingston, Ontario
• OSTI ID: 5654218
• Journal Information: J. Pharmacol. Exp. Ther.; (United States), Vol. 2
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
AORTA
VASODILATION
NITRATES
METABOLISM
CARBON 14 COMPOUNDS
IN VITRO
METABOLITES
MUSCLES
RABBITS
THIN-LAYER CHROMATOGRAPHY
TRACER TECHNIQUES
ANIMALS
ARTERIES
BLOOD VESSELS
BODY
CARDIOVASCULAR SYSTEM
CHROMATOGRAPHY
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NITROGEN COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
SEPARATION PROCESSES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques