Effect of essential fatty acid depletion on tissue phospholipid fatty acids in spontaneously hypertensive and normotensive rats.

Weanling male spontaneously hypertensive (SHR) and normotensive (WKY) rats were maintained on a fat-free semisynthetic diet and killed at various intervals. The effects of fat-depletion on the appearance of essential fatty acid (EFA) deficiency symptoms, the progressive changes of major fatty acids in plasma, liver, heart, and kidney phospholipids (PL), and in skin total lipids were compared between these two strains. After five weeks on the diet, the slower growth and the appearance of EFA deficiency symptoms became evident in SHR. In general, fat-depletion reduced the levels of n-6 fatty acids, whereas it increased those of 20:3n-9. However, the fat-depletion induced reduction of 18:2n-6 in heart PL and 20:4n-6 in kidney, while the elevation of 20:3n-9 in plasma, heart, and kidney PL were greater in WKY than in SHR. As a result, the elevation of biochemical EFA deficiency index--20:3n-9/20:4n-6 ratio--was greater in WKY than in SHR. In comparison with WKY, the concentrations of liver triacylglycerols and the weights of adipose tissues in SHR were reduced to a greater extent, indicating an active catabolism of triacylglycerols in SHR. This study suggests that the earlier appearance of morphological symptoms of EFA deficiency in SHR was not associated with the reducing n-6 EFA levels or with an elevation of triene/tetraene ratio, but possibly to a reduced supply of n-6 EFA for skin prostaglandin synthesis.

Pharmacological manipulation of inflammation in rabbit hydronephrosis: effects of a combined cyclooxygenase/lipoxygenase inhibitor ethoxyquin, a thromboxane synthase inhibitor RS-5186 and a PAF antagonist L-659,989.

The rabbit hydronephrotic kidney (HNK) is a model of renal inflammation characterized by a marked increase in arachidonic acid metabolism that is temporally associated with an inflammatory cell influx into the injured tissue. The HNK exhibits an exaggerated elaboration of eicosanoids ex vivo in response to either bradykinin or the inflammatory cell agonist n-formyl-methionyl-leucyl-phenylalanine (fMLP) compared with the unobstructed contralateral kidney. To pharmacologically manipulate inflammatory cell influx into the HNK we administered ethoxyquin (200 mg/kg p.o.), a combined cyclooxygenase/lipoxygenase inhibitor, RS-5186 (10 mg/kg p.o.), a thromboxane synthase inhibitor or L-659,989 (5 mg/kg p.o.), a platelet activating factor antagonist, before and at various times during the development of hydronephrosis. Only ethoxyquin reduced inflammatory cell influx into the HNK and thereby prevented the enhancement of microsomal cyclooxygenase activity and attenuated the elaboration of eicosanoids ex vivo. Collectively, these results suggest a primary role of an eicosanoid, possibly leukotriene B4, but not thromboxane A2 or the chemotactic phospholipid, platelet activating factor, as a mediator of inflammatory cell influx resulting from ureter obstruction.

Modification of cholesterol crystal-induced inflammation.

Cholesterol crystals induced inflammation in normal rats upon being injected into the footpad. Cholesterol caused less swelling than did an equal amount (3 mg) of monosodium urate crystals. In rats made deficient in essential fatty acids on the basis of clinical criteria (thereby presumably being deficient in prostaglandins) cholesterol crystals did not produce normal levels of swelling. Injections of prostaglandin E1, prostacyclin and thromboxane (B2) did not result in perturbations in cholesterol-induced swelling. Colchicine and indomethacin, given systemically, were very effective in reducing cholesterol crystal-induced foot swelling. Prostaglandin E2 also demonstrated an anti-inflammatory effect.