Weintraub N L, Stephenson A H, Sprague R S, McMurdo L, Lonigro A J
Department of Internal Medicine, St. Louis (Mo) University School of Medicine 63104, USA.
Hypertension. 1995 Oct;26(4):684-90. doi: 10.1161/01.hyp.26.4.684.
In porcine coronary artery endothelium-dependent relaxation to bradykinin is in part attributed to a chemically unidentified factor, termed endothelium-derived hyperpolarizing factor (EDHF). We hypothesize that arachidonic acid, acting through a cyclooxygenase-independent mechanism, is responsible for EDHF production. To define the relationship between EDHF production and arachidonic acid release, we investigated the role of phospholipase C in bradykinin-induced relaxation and prostaglandin I2 production (an index of arachidonic acid release) in porcine coronary artery. The phospholipase C inhibitor U73122 (1 mumol/L) abolished bradykinin-induced, nitric oxide-mediated relaxation but did not inhibit either bradykinin-induced, EDHF-mediated relaxation or prostaglandin I2 production. However, when given at a larger dose (20 mumol/L) U73122 abolished both bradykinin-induced, EDHF-mediated relaxation and prostaglandin I2 production. Similarly, the calcium-ATPase inhibitor thapsigargin, given at a dose (1 mumol/L) that abolished bradykinin-induced increases in intracellular calcium concentration in cultured porcine coronary artery endothelial cells, eliminated both bradykinin-induced. EDHF-mediated relaxation and prostaglandin I2 production. Although thapsigargin abolished bradykinin-induced prostaglandin I2 production, the basal production of prostaglandin I2 was enhanced and contraction of endothelium-intact rings was attenuated. These latter responses are most likely related to enhanced basal arachidonic acid release and associated EDHF production. These observations suggest that phospholipase C activation and increased intracellular calcium concentration are required for both bradykinin-induced arachidonic acid release and EDHF production in porcine coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)
在猪冠状动脉中，内皮依赖性舒张对缓激肽的反应部分归因于一种化学性质不明的因子，称为内皮衍生超极化因子（EDHF）。我们推测，通过不依赖环氧化酶的机制起作用的花生四烯酸负责EDHF的产生。为了确定EDHF产生与花生四烯酸释放之间的关系，我们研究了磷脂酶C在猪冠状动脉缓激肽诱导的舒张和前列腺素I2产生（花生四烯酸释放的指标）中的作用。磷脂酶C抑制剂U73122（1 μmol/L）消除了缓激肽诱导的、一氧化氮介导的舒张，但既不抑制缓激肽诱导的、EDHF介导的舒张，也不抑制前列腺素I2的产生。然而，当给予更大剂量（20 μmol/L）时，U73122消除了缓激肽诱导的、EDHF介导的舒张和前列腺素I2的产生。同样，钙-ATP酶抑制剂毒胡萝卜素以消除缓激肽诱导的培养猪冠状动脉内皮细胞内钙浓度升高的剂量（1 μmol/L）给予时，消除了缓激肽诱导的、EDHF介导的舒张和前列腺素I2的产生。尽管毒胡萝卜素消除了缓激肽诱导的前列腺素I2产生，但前列腺素I2的基础产生增加，内皮完整环的收缩减弱。后一种反应很可能与基础花生四烯酸释放增加和相关的EDHF产生有关。这些观察结果表明，磷脂酶C激活和细胞内钙浓度增加是猪冠状动脉中缓激肽诱导的花生四烯酸释放和EDHF产生所必需的。（摘要截短至250字）
