Vasoactive eicosanoids in the rat heart: clues to a contributory role of cardiac thromboxane to post-ischaemic hyperaemia.

Abstract:

: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.

journal_name

Pharmacol Res

journal_title

Pharmacological research

authors

Giannessi D,Lazzerini G,Sicari R,DeCaterina R

doi

10.1016/1043-6618(92)90233-2

keywords:

subject

Has Abstract

pub_date

1992-12-01 00:00:00

pages

341-56

issue

4

eissn

1043-6618

issn

1096-1186

journal_volume

26

pub_type

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