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Title: Novel mechanisms for buffering the haemodynamic effects of dietary salt and the relevance of skin sodium in humans
Author: Selvarajah, Viknesh
ISNI:       0000 0004 7652 0993
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2018
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Background: Hypertension is one of the most common diseases in the United Kingdom and it remains an important risk factor for cardiovascular morbidity and mortality. Dietary sodium is an important trigger for hypertension and humans show a heterogeneous blood pressure (BP) response to salt intake. The mechanisms for this have not been fully explained, with renal sodium handling thought to play a central role. Animal studies have shown that dietary salt loading results in Na+ accumulation and lymphangiogenesis in skin mediated by vascular endothelial growth factor-C (VEGF-C), both attenuating the rise in BP. This represents an additional system for maintaining BP and volume homeostasis in response to salt load. The focus of this thesis is to determine whether these dermal mechanisms exist in humans. Methods: The technique of measuring skin Na+ and K+ using inductively coupled plasma optical emission spectrometry was developed in a pilot study of healthy adults. In a further study in healthy adults, the effects of dietary salt modulation on skin Na+, the effect of sex and the relationship between skin Na+ and haemodynamic parameters and plasma VEGF-C were studied. Skin Na+ concentrations were expressed as the ratio Na+:K+ to correct for variability in sample hydration. The effect of dietary salt intake on skin gene expression of factors that potentially influence BP such as VEGF-C and the hypoxia inducible factor (HIF) transcription system was assessed, exploring possible mechanisms linking skin Na+ to haemodynamic variables. Results: Skin Na+:K+ increased with dietary salt loading and this effect appeared to be greater in men while only women showed a rise in ambulatory mean BP. Skin Na+:K+ correlated with blood pressure, stroke volume and peripheral vascular resistance in men, but not in women. No change was noted in plasma vascular endothelial growth factor-C. Conclusions: These findings suggest that the skin may buffer dietary Na+, reducing the hemodynamic consequences of increased salt and this may be influenced by sex. Skin Na+ may influence blood pressure, stroke volume and PVR.
Supervisor: Wilkinson, Ian ; McEniery, Carmel Sponsor: British Heart Foundation ; National Institute for Health Research
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: Skin ; sodium ; VEGF-C ; Blood pressure