Relevance of vasoactive mediators for the blood pressure effects of intravenous arachidonic acid injection in rats.
Vasopressor response and release of eicosanoids following intravenous injection of arachidonic acid (AA) were examined in normotensive rats. AA administration caused a rapid initial fall of arterial pressure followed by a brief rise and a subsequent prolonged fall in anesthetized rats. Immediately after AA injection the blood levels of TXB2 and 6-keto-PGF1 alpha, the stable metabolites of TXA2 and prostacyclin, rose, from 1.52 +/- 0.23 ng/ml to 176.4 +/- 42.6 ng/ml and from 4.05 +/- 0.67 ng/ml to 171.4 +/- 31.2 ng/ml, respectively. Blood pressure behaviour and eicosanoid blood level were influenced by different inhibitors and antagonists of vasoactive mediators. The cyclooxygenase inhibitor acetylsalicylic acid completely eliminated the second blood pressure depression after AA injection and simultaneously diminished TXB2 and 6-keto-PGF1 alpha formation in murine blood, whereas the TXA2 receptor antagonist BM 13.177 prevented the return of the blood pressure to preinjection level after the initial brief fall in arterial pressure. Although the TXA2 synthase inhibitor HOE 944 markedly inhibited TXB2 formation, no influence on AA-induced blood pressure changes could be registered. The receptor antagonist of platelet activating factor BN 52021 and the serotonin and histamine receptor antagonist cyproheptadine also reduced TXB2 amounts, in murine blood without any effects on blood pressure behaviour.
Heinroth-Hoffmann
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Department of Pharmacology and Toxicology, Martin Luther University Halle-Wittenberg, Germany.
Giessler
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C
Mest
H J
HJ
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood*; D000818:Animals; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D003533:Cyproheptadine / Q000494:pharmacology; D004224:Diterpenes; D046934:Ginkgolides; D007093:Imidazoles / Q000494:pharmacology; D007275:Injections, Intravenous; D007783:Lactones / Q000494:pharmacology; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood*
D004224:Diterpenes; D046934:Ginkgolides; D007093:Imidazoles; D007783:Lactones; D009281:Naphthalenes; D013449:Sulfonamides; C059526:6-(5-methylimidazol-1-yl)methyl-2-naphthoic acid hydrochloride; D016718:Arachidonic Acid; D003533:Cyproheptadine; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C040624:sulotroban; C045856:ginkgolide B; D001241:Aspirin