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
