6-ketoprostaglandin-f1-alpha and stearic-acid

Obese hypertensives have increased nonesterified fatty acids (NEFAs) and alpha-adrenergic vascular reactivity. Raising NEFAs locally with intralipid and heparin augments dorsal hand venoconstrictor responses to phenylephrine, an alpha(1)-adrenoceptor agonist. The enhanced venoconstrictor responses were reversed by indomethacin. The findings suggest that raising NEFAs leads to the generation of cyclooxygenase (COX) product(s) that enhance vascular reactivity. To test this notion, 6-keto-PGF(1alpha) and TxB(2), the stable metabolites of prostaglandin H(2) (PGH(2)); prostacyclin (PGI(2)); and thromboxane (TxA(2)), were measured approximately 1.5 to 2 cm downstream of a dorsal hand vein infusion of intralipid and heparin (n=10) or saline and heparin (n=5) for 2 hours each. During the third hour, intralipid and heparin (experimental) and saline and heparin (control) were continued, and either saline (control) or indomethacin (intervention) were infused. Intralipid and heparin raised local 6-keto PGF(1alpha) concentrations by 350% to 500% (P<0.005), but saline and heparin did not (P=NS). TxB(2) levels did not change significantly with any infusion. Infusion of indomethacin during the third hour of intralipid and heparin lowered plasma 6-keto-PGF(1alpha) (P<0.05), whereas infusion of saline with intralipid and heparin did not (P=NS). Oleic and linoleic acids at 100 micromol/L, increased 6-keto-PGF(1alpha) in vascular smooth muscle cells (VSMCs) through a protein kinase C and extracellular, signal-regulated kinase independent pathway. However, oleic and linoleic acids increased intracellular Ca(2+) in VSMCs. The data indicate that NEFAs induce the production of COX products, perhaps via Ca(2+)-dependent activation of phospholipase A(2). The COX product(s) may contribute to increased vascular alpha-adrenergic reactivity among insulin-resistant individuals when NEFAs are elevated.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Animals; Calcium; Cells, Cultured; Fat Emulsions, Intravenous; Female; Hand; Heparin; Humans; Indomethacin; Linoleic Acid; Male; Middle Aged; Muscle, Smooth, Vascular; Oleic Acid; Oleic Acids; Rats; Stearic Acids; Thromboxane B2; Time Factors; Veins

The present study compared the effects of diets rich in stearic acid (C18:0) versus one high in lauric and myristic acid (C12:0, C14:0) on platelet phospholipid fatty acid levels and concentrations of urinary thromboxane B2 (TXB2) and 6-keto-PGF1 alpha, which are stable metabolites of thromboxane A2 (TXA2) and PGI2 and indicators of cardiovascular hemostasis. A diet high in dairy butter (B) was the source of C12:0 and C14:0; C18:0 was provided by diets high in cocoa butter (CB), milk chocolate (CHOC) or CB+B in a 4:1 ratio (MIX). A randomized, crossover double-blind experimental design was used. Experimental subjects (n = 15) consumed each diet for 26 days, with a 1-month washout period between each experimental period. Urine and blood were collected from each subject at the beginning and end of each dietary period. Urinary TXB2 and 6-keto-PGF1 alpha were analyzed by radioimmunoassay (RIA). There were no effects of diet on the 24-hour excretion of either metabolite or on the ratio of 6-keto-PGF1 alpha/TXB2, even though there were significant changes in the eicosanoid precursor, arachidonic acid (C20:4n-6), in platelet phospholipids. C20:4n-6 levels increased (44.8% +/- 1.0% to 47.1% +/- 1.3%; P < .05) in the phosphatidylethanolamine phospholipid subclass in subjects on the B diet and decreased in the phosphatidylcholine subclass on the CB diet (16.5% +/- 1.0% to 14.2% +/- 1.1%; P < .05) compared with baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Blood Platelets; Butter; Cacao; Dietary Fats; Double-Blind Method; Epoprostenol; Fatty Acids; Humans; Infant, Newborn; Lauric Acids; Male; Myristic Acid; Myristic Acids; Phosphatidylcholines; Phosphatidylethanolamines; Stearic Acids; Thromboxane A2; Thromboxane B2

The uptake of arachidonate and stearate from serum-free media by endothelial cells was investigated over a 48 h period. Arachidonate was rapidly incorporated into both the phospholipids and triacylglycerols. Triacylglycerol incorporation reached a maximum at 2 h and then rapidly declined with a concomitant increase in phospholipid incorporation. High initial arachidonate incorporation into phosphatidylcholine was followed by a partial transfer of that arachidonate to phosphatidylethanolamine. In contrast, stearate was slowly incorporated into all of the phospholipids and was not incorporated into the triacylglycerols. Cells stimulated with A23187 for 24 h cleaved stearate from all the phospholipids equally, whereas more arachidonate was cleaved from phosphatidylethanolamine than from the other phospholipids. Released arachidonate was both metabolized and reacylated into the triacylglycerols. Our results suggest that triacylglycerols serve as a modulator of intracellular arachidonate concentrations in endothelial cells.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta; Arachidonic Acid; Arachidonic Acids; Calcimycin; Cattle; Cells, Cultured; Endothelium; Kinetics; Phospholipids; Radioimmunoassay; Stearic Acids; Triglycerides