Inorganic Nitrates: Qi for Heart Failure With Preserved Ejection Fraction?

In 1847, the chemist Ascanio Sobrero announced a way to make highly explosive compounds. Among them was nitroglycerin, which he made by heating cellulose in the presence of nitric acid to generate a substance he noted resembled light-yellow olive oil (he was Italian after all). Alfred Nobel subsequently figured out how to stabilize the explosive part, ultimately developing dynamite. This made him rich but reportedly also contrite over the impact his invention had on military operations, leading to his creating the Nobel Prizes as a sort of societal payback. Meanwhile, a Scottish physician, T. Lauder Brunton, was using amyl nitrite to treat angina, and when it was later realized that men with coronary disease working in nitroglycerin and dynamite factories had fewer angina episodes while at work but more over the weekend, its clinical use took off.1 Nitroglycerin is still widely used to treat angina and organo-nitrates, such as isosorbide di-nitrate, and its active metabolite isosorbide mononitrate (ISMN) with longer half-lives are also in clinical use. Article, see p 1151 This is recent history compared with what the Chinese uncovered more than a millennium earlier. They found medicinal value in salpeter (KNO3), an inorganic salt that dissociates in aqueous solution into nitrate anion. As explained in a text attributed to the fifth to sixth century Daoist alchemist and physician Tao Hongjing (Figure), the powder placed under the tongue caused heart qi (figuratively life force) to flow freely and treat chest pain and other conditions of cardiovascular distress.2 In addition to its medical and explosive utility, salpeter was used by the middle ages as a food preservative. The element shared by organo-nitrates, such as nitroglycerin and inorganic KNO3−, is nitrate (NO3−). Nitrate itself has no physiological effects, but must undergo a 3-electron reduction …