Lipid mediators in circulation and hypertension

5 ~ 6周龄自发性高血压大鼠（SHR）的平均动脉血压明显高于Wistar Kyoto大鼠（WKY）。关于SHR中超张力产生的机制，已有大量的研究。在这项研究中，我们的研究重点是血管加压磷脂，溶血磷脂酸（LPA）。在大鼠血浆中，卵磷脂-胆固醇酰基转移酶作用6-12小时形成饱和溶血磷脂酰胆碱。溶血磷脂酶D将溶血磷脂酰胆碱转化为相应的LPAs和不饱和溶血磷脂酰胆碱。SHR中LPAs的产出率显著高于WKY。由于大鼠血浆中溶血磷脂酰胆碱的含量与大鼠血浆中溶血磷脂酰胆碱的含量基本相同，因此大鼠血浆中溶血磷脂酶D的活性高于大鼠血浆。LPA 0.3 ~ 10（ug/kg）可引起清醒大鼠和戊巴比妥麻醉大鼠立即出现高血压和心动过缓。有意识的SHR对LPA的压力反应显著高于WKY，而SHR和WKY对LPA的反应程度相似。接下来，我们观察了LPA在Krebs-Henseleit溶液或Locke溶液中对WKY和SHR胸主动脉离体条的收缩作用。LPA的累积添加没有引起条带收缩。目前，LPA在血液循环中的作用位点尚不清楚。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对心血管的影响的研究结果，以及LPA在SHR血浆中比在WKY血浆中积累得更快的发现，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.