Vasoactive eicosanoids in the rat heart: clues to a contributory role of cardiac thromboxane to post-ischaemic hyperaemia.
To assess the potential role of vasoactive cardiac eicosanoids in the modulation of coronary flow, we measure thromboxane(TX)B2, 6-keto-prostaglandin(PG)F1 alpha, PGE2 and sulphido-peptide leukotrienes (LTC4, D4, E4) in the coronary effluent of isolated perfused rat heart in both baseline and post-ischaemic conditions. Leukotrienes were undetectable. The order of production rate for the other eicosanoids was 6-keto-PGF1 alpha > TXB2 > PGE2. Production of such substances was increased about seven-fold over control after 5 min. global ischaemia; experiments with hypoxia showed that this was due to an actual increase in synthesis and not to a washout effect. A platelet source for TXB2 was excluded by 111In platelet labelling experiments. We assessed relative sensitivity to inhibition of cardiac TX synthesis relative to production of 6-keto-PGF1 alpha to inhibition by aspirin, ibuprofen, diclofenac and the specific thromboxane synthase inhibitor OKY-046. Aspirin, ibuprofen and diclofenac decreased 6-keto-PGF1 alpha production at a concentration always greater than required for a similar extent of TX inhibition. On the other hand a selective inhibition (> 90%) of TX was observed in the presence of OKY-046. Regression analysis of various 6-keto-PGF1 alpha/TXB2 ratios, as obtained in these different conditions, vs coronary flow, showed no correlation in baseline conditions, but a significant positive correlation (r = 0.59, P < 0.01) for post-ischaemic values. These data suggest a role for cardiac eicosanoids, including a non-platelet, cardiac-derived TX, in modulating the hyperaemic response in the isolated rat heart.
Giannessi
D
D
CNR, Institute of Clinical Physiology, Pisa, Italy.
Lazzerini
G
G
Sicari
R
R
DeCaterina
R
R
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D015777:Eicosanoids / Q000096:biosynthesis / Q000502:physiology*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006940:Hyperemia / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D007205:Indium Radioisotopes; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013928:Thromboxane A2 / Q000096:biosynthesis / Q000502:physiology; D013931:Thromboxanes / Q000502:physiology*
D015777:Eicosanoids; D007205:Indium Radioisotopes; D013931:Thromboxanes; D013928:Thromboxane A2