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Historically the treatment for what was called the “hard pulse disease” consisted in reducing the quantity of blood by blood letting or the application of leeches.[1] This was advocated by The Yellow Emperor of China, Cornelius Celsus, Galen, and Hippocrates.[1]In the 19th and 20th centuries, before effective pharmacological treatment for hypertension became possible, three treatment modalities were used, all with numerous side effects: strict sodium restriction (for example the rice diet[1]), sympathectomy (surgical ablation of parts of the sympathetic nervous system), and pyrogen therapy (injection of substances that caused a fever, indirectly reducing blood pressure).[1][14] The first chemical for hypertension, sodium thiocyanate, was used in 1900 but had many side effects and was unpopular.[1] Several other agents were developed after the Second World War, the most popular and reasonably effective of which were tetramethylammonium chloride and its derivative hexamethonium, hydralazine and reserpine (derived from the medicinal plant Rauwolfia serpentina). A major breakthrough was achieved with the discovery of the first well tolerated orally available agents. The first waschlorothiazide, the first thiazide diuretic and developed from the antibiotic sulfanilamide, which became available in 1958;[1][15] it increased salt excretion while preventing fluid accumulation.