Premium
The vasoconstrictor effect of 8‐epi prostaglandin F 2α in the hypoxic rat heart
Author(s) -
Kromer Brendan M,
Tippins John R
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702433
Subject(s) - xanthine oxidase , thromboxane a2 , perfusion , medicine , thromboxane , chemistry , xanthine , endocrinology , xanthine oxidase inhibitor , coronary circulation , receptor , blood flow , biochemistry , platelet , enzyme
8‐epi prostaglandin (PG) F 2α , a vasoconstrictor isoprostane, is synthesized under conditions of oxidative stress. This study was undertaken to investigate the vasoconstrictor effect of 8‐epi PGF 2α in the coronary circulation before and after a period of oxidative stress. The effects of the isoprostane 8‐epi PGF 2α and the thromboxane mimetic U46619 were compared in the isolated rat heart perfused in the Langendorff mode at a constant pressure of 80 mmHg. In normal hearts U46619 caused a dose‐related reduction in coronary flow (ED 50 4.7±2.2 nmol). In contrast, 8‐epi PGF 2α had no effect. After reducing perfusion pressure to 20 mmHg for 30 min and reperfusing at 80 mmHg, the dose‐response curve to U46619 was unaffected. In contrast, 8‐epi PGF 2α caused a dose‐dependent drop in coronary flow (ED 50 52.6±12.7 nmol), producing a similar maximal reduction to U46619. Similarly, after perfusion with xanthine and xanthine oxidase for either 15 or 30 min there was little change in the response to U46619 in comparison to control hearts. In contrast, 8‐epi PGF 2α caused a reduction in coronary flow similar to that produced by U46619, the magnitude of the response being related to the length of xanthine/xanthine oxidase perfusion. Responses to both U46619 and 8‐epi PGF 2α after xanthine/xanthine oxidase perfusion were blocked by the selective thromboxane receptor antagonist SQ29548 10 −7 M . These results show that oxidative stress in the isolated perfused rat heart reveals a potent vasoconstrictor effect of the isoprostane 8‐epi PGF 2α by an action on the thromboxane receptor. The data also suggest that, since 8‐epi PGF 2α is a partial agonist at the thromboxane receptor, thromboxane receptor reserve is increased by oxidative stress.British Journal of Pharmacology (1999) 126 , 1171–1174; doi: 10.1038/sj.bjp.0702433