Effects of arachidonate deficiency on endothelium-dependent vascular reactions.
1. The release of endothelium-derived relaxing factor (EDRF), which appears to be impaired in vessels chronically exposed to hypertension, may involve mobilization of arachidonate from phospholipids. In this study the effects of arachidonate deficiency on endothelium-dependent responses were examined in rat isolated aorta. 2. Weanling rats were fed an essential fatty acid-deficient (EFAD) diet for 8 weeks which reduced plasma and aortic phospholipid arachidonate content from 17 to 1.8% and from 21 to 8%, respectively. After this time the rats were killed and the reactivity of aortic rings was studied in organ baths. 3. In aortic rings from control rats the concentration-response curves for the contractile action of phenylephrine were shifted to the left 3.5-fold by removal of the endothelium, and the maximum was not altered. 4. In contrast, in EFAD rings with endothelium, the maximal vasoconstriction to phenylephrine was less than in control rings, and removal of the endothelium increased the maximum (from 1.9 +/- 0.2 to 3.2 +/- 0.1 g, P less than 0.05) and reduced the EC50 7-fold. 5. In EFAD rings precontracted with phenylephrine (0.3 mumol/l) the relaxations produced by the endothelium-dependent dilator acetylcholine were not significantly different from those produced in control rings. The dilator actions of sodium nitroprusside were also similar in EFAD and control rings. 6. Thus, endothelium-dependent dilatation in the aorta is not impaired by partial depletion of phospholipid arachidonate. However, contractile responses to alpha-adrenoceptor agonists are depressed by spontaneously released EDRF in rat aorta, so that the results suggest that depletion of phospholipid arachidonate either augments spontaneous release of EDRF, or impairs EDRF inactivating mechanisms.
D000818:Animals; D001011:Aorta; D001095:Arachidonic Acids / Q000172:deficiency*; D001688:Biological Products / Q000494:pharmacology*; D002849:Chromatography, Gas; D004041:Dietary Fats / Q000008:administration & dosage; D005227:Fatty Acids / Q000032:analysis; D005228:Fatty Acids, Essential / Q000172:deficiency; D008297:Male; D009569:Nitric Oxide; D010656:Phenylephrine / Q000494:pharmacology; D010743:Phospholipids / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction; D014664:Vasodilation
D001095:Arachidonic Acids; D001688:Biological Products; D004041:Dietary Fats; D005227:Fatty Acids; D005228:Fatty Acids, Essential; D010743:Phospholipids; D010656:Phenylephrine; D009569:Nitric Oxide