Fish oil affects phosphoinositide turnover and thromboxane A metabolism in cultured vascular muscle cells.
Fish oil has been reported as having beneficial effects on cardiovascular diseases. Elevated serum lipoproteins, prostaglandins and intracellular free calcium concentrations [( Ca2+]i) of the vasculature and thus the phosphoinositide (PI) turnover may be involved in the pathogenesis of these disorders. Therefore, the effect of fish oil on the potency of both low-density lipoprotein (LDL) and angiotensin II (AII) to stimulate the PI turnover in cultured rat vascular smooth muscle cells (VSMC) has been studied. Furthermore, a possible link between PI turnover activity and thromboxane A2 (TXA2) metabolism in these cells has been investigated. In VSMC cultured for up to 7 weeks with either fish oil or n-3 eicosapentaenoic acid (EPA) a decrease to 5-48% of the LDL-induced inositol trisphosphate (IP3) formation (= 100%) was found. A similar range of decreased IP3 synthesis was observed, when AII was used instead of LDL. Both LDL- and AII-stimulated TXA2 synthesis was suppressed concomitantly within the range 34-60%. Blockade of VSMC TXA2 biosynthesis with either indomethacin or TXA2 synthetase blocker (SQ-80338) inhibited LDL-induced formation of IP3 in a dose-dependent manner. Similar results were obtained, when TXA2 receptor coupling antagonists (SQ-27427 or BM-13177) were used. However, blockers of TXA2 synthesis and of TXA2 receptor binding failed to affect AII-induced formation of IP3.
Locher
R
R
Department of Internal Medicine, University Hospital, Zürich, Switzerland.
Sachinidis
A
A
Steiner
A
A
Vogt
E
E
Vetter
W
W
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D005395:Fish Oils / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007295:Inositol Phosphates / Q000096:biosynthesis / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D013928:Thromboxane A2 / Q000096:biosynthesis / Q000378:metabolism*
D005395:Fish Oils; D007295:Inositol Phosphates; D008077:Lipoproteins, LDL; D010716:Phosphatidylinositols; D000804:Angiotensin II; D013928:Thromboxane A2; D015118:Eicosapentaenoic Acid; D007213:Indomethacin