Lipid mediators in circulation and hypertension

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Mean arterial blood pressures of spontaneously hypertensive rats(SHR) 5-6 weeks old are significantly higher than those of Wistar Kyoto rats (WKY). Numerous numbers of studies concerning the mechanisms of hyper-tension in SHR have been drawn. In this study,we focussed our interest on a vasopressor phospholipid,lysophosphatidic acid(LPA).In rat plasma,saturated lysophosphatidylcholines were formed by the action of lecithin-cholesterol acyltransferase during 6-12 hours incubation. The lysophosphatidylcholines were converted into the corresponding LPAs by lysophospholipase D as well as unsaturated lysophosphatidylcholines. The rates of productions of LPAs in SHR were significantly higher than those in WKY. Because the levels of lysophosphatidylcholines in fresh plasma from SHR were almost the same as those from WKY,the activity of lysophospholipase D in SHR plasma was suggested to be higher than that of WKY.LPA 0.3-10(ug/kg)induced an immediate hypertension and bradycardia both in conscious rats and pentobarbital-anesthetized rats. The pressor responses to LPA of conscious SHR was significantly higher than those of WKY,whereas both SHR and WKY responded to LPA in similar extents.Next,we examined contractile action of LPA on isolated strips of thoracic aorta of WKY and SHR in Krebs-Henseleit solution or Locke solution. Cumulative addition of LPA induced no contraction of the strips.At present,the sites of actions of LPA in the circulation remains unclear. Some kinds of vascular smooth muscle cells other than thoracic aorta might be more responsive to LPA than those of WKY. Our results on cardiovascular effects of LPA together with the finding that LPA accumulated more rapidly in SHR plasma than in WKY plasma,indicated that this physiologically active phospholipid is involved in an early phase of hypertension in SHR.