Plant-Derived Substances and Cardiovascular Diseases : Effects of Flavonoids, Terpenes and Sterols on Angiotensin-Converting Enzyme and Nitric Oxide

Abstract: Diet has for many years been known to play a key role in the development of chronic diseases. There are clear associations between consumption of vegetables, fruits and berries, and risk of cardiovascular diseases, the number one cause of death in the world. To maintain homeostasis of the vascular wall the balance between angiotensin II, nitric oxide and reactive oxygen species is of great importance in order to affect the development of cardiovascular diseases. Angiotensin II, a potent vasoconstrictor causing cell growth and nitric oxide, a signalling molecule influencing the vascular system as a vasodilatator, inhibiting cell proliferation and reactive oxygen species, are linked together in the renin-angiotensin aldosteron system. Angiotensin-converting enzyme will as a key enzyme in the reninangiotensin aldosteron system convert angiotensin I to form angiotensin II and nitric oxide is known to inhibit angiotensin-converting enzyme and act as a scavenger of reactive oxygen species. Plant-derived substances as flavonoids, tocopherols and carotenoids are shown to have beneficial effects on the cardiovascular system due to their antioxidative effects. The aims of this study were to investigate beverages, dietary products, herbal medicinal plants, α-tocopherol, β-carotene, sterols and lipidowering drugs on angiotensin-converting enzyme activity and nitric oxide concentrations. This was done to investigate if the sole mechanism of plant-derived substances is their antioxidative properties and to investigate if there is any connection between effect and biosynthesis/structure of plant substances. The tested infusions and extracts containing high amounts of flavonoids, the flavonoids and β-carotene significantly inhibited angiotensin-converting enzyme activity in vitro. The other substances tested did not affect, or in some cases significantly increased, angiotensin-converting enzyme activity. The infusions and extracts containing high amounts of flavonoids, the flavonoids andβ-carotene showed an increase on nitric oxide concentrations in vitro. Oral intake of a single dose of Rooibos tea significantly inhibited angiotensin-converting enzyme activity. A significant inhibition of angiotensin-converting enzyme activity was seen with the green tea for the angiotensin-converting enzyme genotypes II and ID. A significant inhibition of angiotensin-converting enzyme activity was also seen with the Rooibos tea for the angiotensin-converting enzyme genotype II.Conclusion; flavonoids and β-carotene interact with the cardiovascular system in severalways, by reducing reactive oxygen species (as shown in several studies), increasing nitricoxide concentrations (as shown here and by others) and also by inhibiting angiotensinconvertingenzyme activity (as shown here). Infusions and extracts as tea containing highamounts of flavonoids function as angiotensin-converting enzyme inhibitors. Angiotensinconvertingenzyme contains two zink-dependent catalytic domains and angiotensinconvertingenzyme inhibitors are designed to bind to the Zn2+ at the active site. If theinhibitory mechanism of flavonoids on angiotensin-converting enzyme activity is due to theirability to bind to Zn2+ ions then it would be possible for the flavonoids to also inhibit otherzinc metallopeptidases, i.e. endothelin-converting enzyme, matrix metallopeptidases, neutralendopeptidase and maybe insulin-degrading enzyme, thereby exerting several additionalpositive effects on the cardiovascular system.