Recent dietary epidemiological and intervention studies in humans and animals indicate that cocoa and other foods and beverages that are rich in flavanols as tea and wine, can benefit cardiovascular function, inclusive regulating blood pressure. We propose that the antihypertensive effects of flavanols are, in part, mediated by an inhibition of the angiotensin converting enzyme (ACE). This is hypothesized based on our results showing that: a) dietary flavanols can be absorbed and are present in blood; b) flavanols and their oligomers (procyanidins) can compete with angiotensin and other substrates and inhibit ACE; c) ACE modulates reactive oxygen species (ROS) and nitric oxide (NO) production. In addition, considering that NO is a molecule directly involved in blood pressure control, and that NO metabolism is directly affected by both, ROS and flavanols, we propose to investigate how a flavanol-inhibition of ACE affects blood pressure and ROS and NO metabolism.
The specific aims of this proposal are: 1) characterize the effect of a flavanol- rich diet on ACE activity in hypertensive Goldblatt 2K1C rats (2K1C rats); and 2) characterize the effects of flavanols and related compounds on ACE, and ROS and NO metabolism in cultured human umbilical vein endothelial cells (HUVEC).
For aim 1, hypertensive 2K1C rats will be fed a purified control diet added with a well defined flavanol-rich cocoa powder and we will determine the effects of this dietary intervention on blood pressure, heart weight and on ACE activity and protein, angiotensin I and angiotensin II, as well as markers of ROS and NO metabolism in blood, kidneys, and aorta.
For specific aim 2, HUVEC will be exposed to flavanols or related compounds, and then incubated with angiotensin I (ACE substrate) and angiotensin II (ACE product). Flavanols effects will be evaluated by determining ACE activity, RNA and protein, ACE-mediated cell oxidation, and NO metabolism. Integrating rat and endothelial cell results, we expect to advance the knowledge of how flavanol-containing nutrients could be involved in the prevention or progression of hypertension and renin-angiotensin system-associated pathologies. In brief, we will provide evidence that certain components of cocoa, the flavanols, have beneficial health effects, decreasing blood pressure and organ oxidation based on ACE inhibition. This could allow the development of simple and non- expensive strategies aimed to control hypertension and other disorders related to ROS and NO metabolism.
| Galleano, Monica; Oteiza, Patricia I; Fraga, Cesar G (2009) Cocoa, chocolate, and cardiovascular disease. J Cardiovasc Pharmacol 54:483-90 |
| Fraga, Cesar G (2007) Plant polyphenols: how to translate their in vitro antioxidant actions to in vivo conditions. IUBMB Life 59:308-15 |
