Lipid mediators in circulation and hypertension

5~6周龄自发性高血压大鼠(SHR)的平均动脉压显著高于Wistar京都大鼠(WKY)。大量关于自发性高血压的高血压机制的研究已经被提出。在这项研究中，我们的兴趣集中在一种血管加压磷脂，溶血磷脂酸(LPA)。在大鼠血浆中，饱和的溶血磷脂酰胆碱是由卵磷脂-胆固醇酰基转移酶在孵育6-12小时内形成的。溶血磷脂酶D和不饱和溶血磷脂酰胆碱将溶血磷脂酰胆碱转化为相应的LPA。SHR的LPA生成率显著高于WKY。由于SHR新鲜血浆中溶血磷脂酰胆碱的水平与WKY几乎相同，故SHR血浆中溶血磷脂酶D的活性高于WKY。LPA 0.3-10(ug/kg)在清醒大鼠和戊巴比妥钠麻醉大鼠均可引起即刻高血压和心动过缓。清醒SHR对LPA的升压反应显著高于WKY，而SHR和WKY对LPA的反应相似。LPA的累积添加没有引起血管收缩。目前，LPA在循环中的作用部位尚不清楚。除胸主动脉外，某些血管平滑肌细胞对LPA的反应可能比WKY更敏感。我们关于LPA心血管效应的结果，以及LPA在SHR血浆中比在WKY血浆中蓄积更快的发现，表明这种生理活性磷脂参与了SHR高血压的早期阶段。

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.