Decreased pulmonary vascular responsiveness in rats raised on an essential fatty acid deficient diet.
Leukotriene C4 is produced during hypoxic pulmonary vasoconstriction and leukotriene inhibitors preferentially inhibit the hypoxic pressor response in rats. If lipoxygenase products are important in hypoxic vasoconstriction, then an animal deficient in arachidonic acid should have a blunted hypoxic pressor response. We investigated if vascular responsiveness was decreased in vascular rings and isolated perfused lungs from rats raised on an essential fatty acid deficient diet (EFAD) compared to rats raised on a normal diet. Rats raised on the EFAD diet had decreased esterified plasma arachidonic acid and increased 5-, 8-, 11-eicosatrienoic acid compared to rats raised on the normal diet (control). Compared to the time matched responses in control isolated perfused lungs the pressor responses to angiotensin II and alveolar hypoxia were blunted in lungs from the arachidonate deficient rats. This decreased pulmonary vascular responsiveness was not affected by the addition of indomethacin or arachidonic acid to the lung perfusate. Similarly, the pulmonary artery rings from arachidonate deficient rats demonstrated decreased reactivity to norepinephrine compared to rings from control rats. In contrast, the tension increases to norepinephrine were greater in aortic rings from the arachidonate deficient rats compared to control. Stimulated lung tissue from the arachidonate deficient animals produced less slow reacting substance and platelet activating factor like material but the same amount of 6-keto-PGF1 alpha and TXB2 compared to control lungs. Thus there is an association between altered vascular responsiveness and impairment of stimulated production of slow reacting substance and platelet activating factor like material in rats raised on an EFAD diet.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D001835:Body Weight; D004041:Dietary Fats / Q000008:administration & dosage*; D005231:Fatty Acids, Unsaturated / Q000097:blood; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D010972:Platelet Activating Factor / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
D001095:Arachidonic Acids; D004041:Dietary Fats; D005231:Fatty Acids, Unsaturated; D010972:Platelet Activating Factor; D013189:SRS-A; D016718:Arachidonic Acid