RELEASE OF MARKEDLY INCREASED QUANTITIES OF PROSTAGLANDIN-D2 INVIVO IN HUMANS FOLLOWING THE ADMINISTRATION OF NICOTINIC-ACID
RELEASE OF MARKEDLY INCREASED QUANTITIES OF PROSTAGLANDIN-D2 INVIVO IN HUMANS FOLLOWING THE ADMINISTRATION OF NICOTINIC-ACID
复制标题
DOI：
10.1016/0090-6980(89)90088-9
复制
发表时间：
1989-08-01
影响因子：
2.9
通讯作者：
ROBERTS, LJ
中科院分区：
文献类型：
--
作者：
MORROW, JD;PARSONS, WG;ROBERTS, LJ
烟酸（烟酸）是一种 B 族维生素，也是一种有效的降血脂剂。然而，摄入药理剂量的烟酸后会出现强烈的潮红，这极大地限制了其治疗高脂血症的有效性。先前的研究表明，烟酸引起的潮红可以通过环氧合酶抑制剂预处理而大大减弱，这表明血管舒张是由前列腺素介导的。然而，可能介导潮红的前列腺素尚未最终确定。在这项研究中，我们报告了这样的发现：摄入烟酸会引起人体内 PGD2 释放量显着增加。通过气相色谱质谱法对血浆中的PGD2代谢物9α、11β-PGF2进行定量来评估PGD2释放。三名正常志愿者摄入 500 mg 烟酸后，出现强烈潮红，并且发现 9α、11β-PGF2 的血浆水平急剧增加 800、430 和 535 倍。 9α、11β-PGF2 的水平在 12 至 45 分钟之间达到最大值。摄入烟酸后，2-4小时内下降至接近正常水平。血浆中 9α、11β-PGF2 的水平与 3 名志愿者发生的潮红强度和持续时间相关。 PGD2的释放不伴随组胺的释放，组胺的释放通过组胺代谢物N.tau.-甲基组胺的血浆水平的定量来评估。这表明 PGD2 释放的来源不是肥大细胞。摄入烟酸后，前列环素代谢物 2,3-dinor-6-keto-PGF1.α 的尿排泄量仅略有增加（约 2 倍），而主要尿代谢物 PGE2 的排泄量并未增加。这些结果表明摄入烟酸后释放的主要血管舒张PG是PGD2。 PGD2 释放量显着增加的事实表明，PGD2 是烟酸诱导的人类血管舒张的介质。
Nicotinic acid (niacin) is a B vitamin which is also a potent hypolipidemic agent. However, intense flushing occurs following ingestion of pharmacologic doses of niacin which greatly limits its usefulness in treating hyperlipidemias. Previous studies have demonstrated that niacin-induced flushing can be substantially attenuated by pre-treatment with cylooxygenase inhibitors, suggesting that the vasodilation is mediated by a prostaglandin. However, the prostaglandin that presumably mediates the flush has not been conclusively determined. In this study we report the finding that ingestion of niacin evokes the release of markedly increased quantities of PGD2 in vivo in humans. PGD2 release was assessed by quantifiation of the PGD2 metabolite, 9.alpha., 11.beta.-PGF2, in plasma by gas chromatography mass spectrometry. Following ingestion of 500 mg niacin in three normal volunteers, intense flushing occurred and plasma levels of 9.alpha., 11.beta.-PGF2 were found to increase dramatically by 800, 430, and 535-fold. Levels of 9.alpha., 11.beta.-PGF2 reached a maximum between 12 and 45 min. after ingesting niacin and subsequently declined to near normal levels by 2-4 hours. Levels of 9.alpha., 11.beta.-PGF2 in plasma correlated with the intensity and duration of flushing that occurred in the 3 volunteers. Release of PGD2 was not accompanied by a release of histamine which was assessed by quantification of plasma levels of the histamine metabolite, N.tau.-methylhistamine. This suggest that the origin of the PGD2 release is not the mast cell. Only a modest increase (approximately 2-fold) in the urinary excretion of the prostacyclin metabolite, 2,3-dinor-6-keto-PGF1.alpha., occurred following ingestion of niacin and no increase in the excretion of the major urinary metabolite of PGE2 was found. These results indicate that the major vasodilatory PG released following ingestion of niacin is PGD2. The fact that markedly increased quantities of PGD2 are released suggests that PGD2 is the mediator of niacin-induced vasodilation in humans.