Circulating prostacyclin metabolites in the dog.

Area of Science:

• Pharmacology
• Biochemistry
• Analytical Chemistry

Background:

• Prostacyclin (PGI2) is a crucial vasodilator and inhibitor of platelet aggregation.
• Understanding PGI2 metabolism is vital for assessing its physiological and pathological roles.
• Accurate measurement of PGI2 metabolites is necessary to evaluate its in vivo activity.

Purpose of the Study:

• To quantify prostacyclin (PGI2) metabolites in canine blood following intravenous administration.
• To identify and characterize the temporal changes in PGI2 metabolite concentrations.
• To determine which metabolites best reflect circulating PGI2 levels.

Main Methods:

• Intravenous administration of radiolabeled prostacyclin ([11 beta-3H]PGI2) to five dogs.
• Serial blood sampling over 120 minutes post-administration.
• Analysis of plasma radioactivity using two-dimensional thin-layer chromatography and radio-high-performance liquid chromatography.
• Identification of metabolites by comparison with synthetic standards.

Main Results:

• Seven PGI2 metabolites were identified, including 6-keto-PGF1α and various dinor and tetranor derivatives.
• Early plasma samples were rich in 6-keto-PGF1α and other 20-carbon metabolites.
• By 30 minutes, 16- and 18-carbon dicarboxylic acids became predominant.
• By 60 minutes, two unidentified polar compounds constituted 85% of the radioactivity.

Conclusions:

• 6-keto-PGF1α likely represents transient PGI2 entry into circulation.
• More polar metabolites, such as 2,3,18,19-tetranor-13,14-dihydro-6,15-diketo-20-carboxyl PGF1α, may serve as more reliable indicators of overall PGI2 presence due to their longer half-lives.
• This research provides insights into canine PGI2 pharmacokinetics and metabolite profiles.