3-4-dihydroxyphenylpropionic-acid and Hypertension

We report new examples of a series of losartan-hydrocaffeic hybrids that bear novel ester, amide and amine linkers. These compounds were made by linking hydrocaffeic acid to the side chain of losartan at the C-5 position of the imidazole ring through different strategies. Experiments performed in cultured cells demonstrate that these new hybrids retain the ability to block the angiotensin II effect and have increased antioxidant ability. Most of them reduced arterial pressure in rats better or as much as losartan.

Topics: Amides; Amines; Angiotensin II; Animals; Antihypertensive Agents; Antioxidants; Aorta, Thoracic; Caffeic Acids; Cells, Cultured; Esters; Hypertension; Losartan; Male; Molecular Structure; Muscle, Smooth, Vascular; Rats; Rats, Wistar; Structure-Activity Relationship; Vasoconstrictor Agents

We report the first examples of a new series of antioxidant-sartan hybrids (AO-sartans), which were made by adding an antioxidant fragment to the hydroxymethyl side chain of losartan. Experiments performed in cultured cells demonstrate that these new hybrids retain the ability to block the angiotensin II effect with increased antioxidant ability. In hypertensive rats, these compounds show properties that suggest they may be more useful than losartan for controlling hypertension and preventing hypertension-induced cardiovascular damage.

Topics: Alcohols; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Antioxidants; Blood Pressure; Cardiovascular Diseases; Cells, Cultured; Collagen Type I; Esters; Fibronectins; Humans; Hypertension; Losartan; Male; Oxidative Stress; Rats; Rats, Wistar