Inorganic nitrate for blood pressure lowering?

Letters to the Editor will be published, if suitable, as space permits. They should not exceed 1000 words (typed double-spaced) in length and may be subject to editing or abridgment. Kapil et al 1 reported that potassium nitrate ingestion lowers blood pressure (BP) in human subjects. Peak plasma nitrate (NO 3 Ϫ) and nitrite (NO 2 Ϫ) concentrations increased up to 35-and 4-fold, respectively. Increased plasma cGMP levels suggests that the depressor action of nitrate is mediated by the NO/cGMP cascade, presumably after reduction of NO 3 Ϫ to NO 2 Ϫ and its reduction to NO. Using 15 NO 3 Ϫ , we provided evidence for 15 NO 3 Ϫ to 15 NO 2 Ϫ reduction in humans. 2 Similar results were obtained for 15 NO 3 Ϫ and S-[ 15 N]nitroso-N-acetylcysteine ethyl ester in male rabbits (Figure). Oral administration of isosorbide dinitrate (ISDN) (0.13 mmol daily) and pentaerythrityl tetranitrate (PETN) (0.25 mmol daily) increased moderately plasma concentration of NO 3 Ϫ (1.2-and 1.4-fold, respectively) and NO 2 Ϫ (2.2-and 1.8-fold, respectively) in young subjects. 3 Organic nitrates (R-ONO 2), inorganic salts of NO 3 Ϫ and NO 2 Ϫ , and thionitrites (R-SNO) seem to lower BP through similar mechanisms, but their pharmacokinetics and pharmaco-dynamics differ considerably. The single dose of 0.32 to 0.45 mmol NO 3 Ϫ /kg 1 is up to 60 times the mean daily endoge-nous NO synthesis rate in healthy subjects and up to 36 times the therapeutic ISDN and PETN dose. 3 NO 3 Ϫ required for BP lowering results in very high and long-lasting extracellular and intracellular NO 3 Ϫ and NO 2 Ϫ concentrations, which may, in turn, exert toxic, mutagenic, and cancerogenic effects. NO 3 Ϫ and NO 2 Ϫ are actively transported in various cells including the nephron. 2 High millimolar tissue concentrations of NO 3 Ϫ may induce acidosis in mammalian cells. 4 Also, elevation of methemo-globin, oxidative stress, and glutathione consumption may ensue.