Masters Degrees (Medical Physiology)

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Browsing Masters Degrees (Medical Physiology) by browse.metadata.advisor "Bester, Dirk"

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    The treatment effect of Rooibos on vascular function and signalling pathways of aortas from diet induced obese rats.
    (Stellenbosch : Stellenbosch University, 2017-03) Eldieb, Nada Ahmed; Marais, Erna; Bester, Dirk; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Medical Physiology
    ENGLISH ABSTRACT : Introduction: Obesity is becoming a worldwide health problem and is a well-documented independent risk factor for the development of endothelial dysfunction (decreased nitric oxide (NO) bioavailability) and cardiovascular disease (CVD). It is also associated with chronic inflammation and decreased insulin sensitivity. As a highly active endocrine organ, perivascular adipose tissue (PVAT) releases a variety of adipokines and inflammatory cytokines that activate several signalling pathways. Recently, observational studies have indicated a role for oral supplementation of Rooibos (RB) in lowering the risk for cardiovascular disease by improving endothelial dysfunction by means of RB’s anti-inflammatory and anti-oxidant properties. The acute effect of RB in an ex vivo aortic model has not been investigated yet. Aims: Therefore, this study aimed to investigate the effect of direct RB administration to aortas from obese and lean Wistar rats, by measuring the aortic function as well as changes in the signalling pathways and the inflammatory markers. . Methods: Aortas were obtained from three groups of euthanized male Wistar rats: young control (aged 16 weeks), aged-matched lean group (aged 22 weeks) on a normal rat chow and diet group (aged 22 weeks) on a 16 week high fat diet, HFD (high in sucrose and cooking fat). Aortic segments, with or without PVAT, were placed into an organ bath containing Krebs buffer at 37⁰C. Aortic ring function was determined by cumulative phenylephrine (PE) induced contraction (PE: 100nM-1μM), followed by cumulative acetylcholine (Ach) induced relaxation (Ach: 30 nM-10μM). RB (0.02%) was administered for 30 min during stabilisation before initiation of contraction and relaxation. Intracellular signalling pathways: eNOS, and the upstream activators PKB and AMPK, MAPKs (ERK1/2, JNK1/2, P38), as well as Nitrotyrosine and CREB were evaluated using Western blot analysis. Inflammatory markers were also analysed using the multiplex kit. Data was analysed using two-way ANOVA with Bonferroni’s post-test. Results: The HFD caused an increase in body weight, intraperitoneal fat, fasting glucose level, as well as HOMA index. Aortas with PVAT of the older lean group showed a significant increase in contractility compared to the young control (p <0.05). However aortas with PVAT of the obese diet group showed a reduced contractile response and enhanced relaxation response compared to the lean group (p <0.05). The addition of RB decreased the contractile response in lean group with PVAT. However, RB enhanced the contractility of the diet group (with and without) PVAT, as well as reduction in relaxation on the diet group without PVAT. The diet group had increased phosphorylation and phospho/total ratio of eNOS and ERK1/2 in aortas with and without PVAT, compared to the lean group. However, RB decreased this effect. Inflammatory markers showed variable results. Conclusion: Sixteen weeks on a HFD was effective to induce insulin resistance. The anti-contractile effect of the HFD on aortic function and the enhancement in the relaxation might be due to the elevation of phosphorylated eNOS that was associated with increased ERK1/2 phosphorylation. This study demonstrated that RB may reverse the contractile inhibition of obese rat aorta with PVAT, with no effect on PVAT relaxation. Furthermore, RB has shown a pro-contractile and anti-relaxant effect in aorta of the diet group without PVAT. This demonstrates that RB in not deleterious when PVAT is present and may be beneficial to endothelial function in obese individuals.