Release of markedly increased quantities of prostaglandin D2 [formula omitted] in humans following the administration of nicotinic acid

Abstract

Nicotinic acid (niacin) is a B which is also a potent hypolipidemic agent. However, intense flusing occurs following ingestion of harmacology doses of niacin which greatly limits its usefulness in treating hyperlipidemias. Previous studies have demonstrated that niacin-induced flusing can be substantially attenuated by pre-treatment with cyclooxygenase inhibitors, suggesting that the vasodilation is mediated by a prostaglandin. However, the prostaglandin that presumably mediates the flush has not bee conclusively determined. In this study we report the finding that ingestion of niacin evokes the release of markedly increased quantities of PGD 2 in vivo in humans. PGD 2 release was assessed by quantification of PGD 2 metabolite, 9α 11β-PGF 2, in plasma by gas chromatography mass spectrometry. Following ingestion of 500 mg of niacin in three normal volunteers, intense flushing occurred and plasma levels of 9α, 11β-PGF 2 were found to increase dramatically by 800, 430, and 535-fold. Levels of 9α,11β-PGF 2 reached a maximum between 12 and 45 min. after ingesting niacin and subsequently declined to near normal levels by 2–4 hours. Levels of 9α, 11β-PGF 2 in plasma correlated with the intensity and duration of flushing that occurred in the 3 volunteers. Release of PGD 2 was not accompanied by a release of histamine which was assessed by quantification of plasma levels of the histamine metabolit, N τ-methylhistamine. The suggests that the origin of the PGD 2 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-PGF 1α, occurred following ingestion of niacin and no increase in the excretion of the major urinary metabolite of PGE 2 was found. These results indicate that the major vasodilatory PG released following ingestion of niacin is PGD 2. The fact that markedly increased quantities of PGD 2 are released suggests that PGD 2 is the mediator of niacin-induced vasodilation in humans.