title: Impacts of whole grain oats intake on blood pressure and vascular function; the role of phenolic acids on the renin angiotensin system
Creators: name: Al Sharif, Sarah
Publisher: name: University of Reading
Year: 2018

description: Hypertension is a major risk factor for cardiovascular disease and there is substantial evidence that its reduction towards the normotensive state significantly reduces the risk of developing cardiovascular morbidity and mortality. In addition to pharmacological treatment of hypertension, diet is also capable of counteracting the development of high blood pressure and reducing it from an elevated state. Diets rich in plant foods have been found to attenuate blood pressure rises over time and a number of polyphenol-rich foods/beverages derived from plants have been shown to induce beneficial effects on endothelial function and blood pressure in human clinical trials. Polyphenol rich foods include many fruits and vegetables, cocoa, tea, coffee and their derived extracts. Less is known regarding other polyphenol-rich staple foods, such as whole grains which also contain relatively high levels of these bioactives. Whole grain oats are a rich source of small phenolic compounds, such as ferulic acid and avenanthramides, in addition to their widely recognised fibre content, so may also be capable of beneficial changes to endothelial function and blood pressure. This thesis tests this hypothesis and attempts to understand the actions of small phenolics and their metabolites from oats on the renin-angiotensin aldosterone system (RAAS), a major regulator of human blood pressure homeostasis. To investigate the actions of the most abundant oat phenolics on the RAAS, we utilised kidney juxtaglomerular and HUVEC cells to test whether they and their metabolites influenced renin expression and whether this was regulated via interactions with the ERK-CRB/ATF pathway. Renin gene expression was significantly decreased by exposure to several polyphenols, including avenanthramides (AV-B) and phenolic acid (as trans-Ferulic Acid). Expression was modulated by significant inhibition of CREB, ERK and ATF transcription factors, which occurred when treated with any of the polyphenols. However, although we found small changes, contrary to some published studies, we found no significant inhibition of ACE activity via this mechanism, nor any significant increases in total NO, nitrite or nitrate. Therefore, we did not find conclusively that polyphenols reduce BP via the RAAS, however, we suggest that higher doses should be tested, as they may result in ACE inhibition. In an acute randomised controlled crossover intervention trial (RCT) oat intake (90.2 g oats containing 50 mg phenolic acid) improved % FMD, however, while the improvements may have been medically relevant, they were not significant and were, therefore, inconclusive. Similarly, secondary outcomes including, notably, blood pressure and endothelium-independent vasodilation at early time points tended towards improvement; but the trials were not assessed for power against secondary outcomes which, along with the lack of significance in the primary outcomes, prevents conclusions being drawn based on these results. Similar outcomes which may signify lower stress on the vascular systems of the subjects, but were not statistically significant, were found from a chronic trial, where volunteers consumed different levels of oat based avenanthramides and phenolic acids. In particular, 24 hour ambulatory blood pressure and % FMD responses improved, as did night-time systolic blood pressure, which reduced by 5.1 mm Hg following a high phenolic oat intervention. High phenolic oats interventions also led to decreases in daytime and 24 h SBP by 0.15 and 1.16 mm Hg respectively and increased endothelial microvascular reactivity. We conclude that there while there were indications of positive, medically relevant differences in vascular function, following both acute and chronic trials, none was statistically significant. The most marked improvements were seen in endothelium-independent blood flow at 2 h post consumption in the acute trial and lowered 24 h ambulatory BP in the chronic trial. The relatively short duration of the trials or likely too small, insufficiently powered sample sizes may have been responsible for the lack of conclusive statistical evidence.