Craven P A, Studer R K, DeRubertis F R
Department of Medicine, University of Pittsburgh, Pennsylvania.
Hypertension. 1990 Apr;15(4):388-96. doi: 10.1161/01.hyp.15.4.388.
The capacity of cultured renal medullary interstitial cells derived from Dahl salt-sensitive and salt-resistant rats to synthesize prostaglandin E2 (PGE2) was compared. Basal and arginine vasopressin (AVP)-induced PGE2 production by interstitial cells from salt-resistant rats was fourfold to fivefold higher than corresponding values of those from the salt-sensitive rats. Similarly, basal and AVP-responsive release of [3H]arachidonate were twofold higher by interstitial cells from salt-resistant compared with salt-sensitive rats. Differences in PGE2 production were abolished by the calcium inophore A23187 or the addition of exogenous arachidonate. The latter findings suggested a role for altered availability of endogenous arachidonate, possibly mediated by reduced calcium-responsive lipase activity. Basal and AVP-induced increases in cytosolic free calcium concentration, assessed by the aequorin method, were significantly lower in interstitial cells from salt-sensitive versus salt-resistant rats, further supporting a possible role for altered cellular calcium homeostasis. Studies of the potential contribution of various phospholipases and of triglyceride lipase to the release of arachidonate for PGE2 synthesis in interstitial cells implicated phospholipase A2 activity as a major pathway. When assessed in vitro in cell cytosolic fractions at identical calcium concentration, phospholipase A2 activity was lower in interstitial cells from salt-sensitive versus salt-resistant rats. Thus, both reduced cytosolic free calcium and phospholipase A2 activity of interstitial cells from salt-sensitive rats may contribute to the diminished capacity of these cells to liberate endogenous arachidonate for PGE2 synthesis.
比较了源自 Dahl 盐敏感型和盐抵抗型大鼠的培养肾髓质间质细胞合成前列腺素 E2（PGE2）的能力。盐抵抗型大鼠间质细胞的基础和精氨酸加压素（AVP）诱导的 PGE2 生成量比盐敏感型大鼠相应的值高 4 至 5 倍。同样，与盐敏感型大鼠相比，盐抵抗型大鼠间质细胞的基础和 AVP 反应性 [3H]花生四烯酸释放量高 2 倍。钙离子载体 A23187 或添加外源性花生四烯酸消除了 PGE2 生成的差异。后一发现提示内源性花生四烯酸可用性改变可能起作用，可能由钙反应性脂肪酶活性降低介导。通过水母发光蛋白法评估，盐敏感型大鼠间质细胞的基础和 AVP 诱导的细胞溶质游离钙浓度增加显著低于盐抵抗型大鼠，进一步支持细胞钙稳态改变可能起作用。对各种磷脂酶和甘油三酯脂肪酶对间质细胞中花生四烯酸释放以合成 PGE2 的潜在贡献的研究表明磷脂酶 A2 活性是主要途径。在相同钙浓度下在细胞溶质部分进行体外评估时，盐敏感型大鼠间质细胞的磷脂酶 A2 活性低于盐抵抗型大鼠。因此，盐敏感型大鼠间质细胞的细胞溶质游离钙减少和磷脂酶 A2 活性降低都可能导致这些细胞释放内源性花生四烯酸以合成 PGE2 的能力下降。
