Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.689172
Title: Ethnic differences in low renin status, vascular function and renal salt handling
Author: Connell, Kenneth Leon
ISNI:       0000 0004 5917 8882
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2015
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Abstract:
Sodium retention with suppressed plasma renin activity (PRA) is more common in black subjects of African ancestry compared to white subjects and is associated with an increased propensity to the development of hypertension. This thesis investigates whether such low renin status might be secondary to reduced availability of endothelium-derived or other peri-renal tubular source of nitric oxide (NO). The association of flow-mediated dilation (FMD, a measure of the vasomotor response to endothelium-derived NO) to PRA was examined in a group of asymptomatic subjects (n=143) of African/African-Caribbean (n=84, classified as “Black”) and White European (n=59) self-defined ethnic groups. The effects of a change in salt intake on FMD were examined in a subset of 21 subjects and effects of inhibition of NO synthase on urinary sodium excretion were examined in a sub-set of 40 subjects. FMD was positively correlated with PRA, independent of age, gender, Black/White ethnicity, 24- hour urinary sodium excretion and blood pressure (standardised regression coefficient, β= 0.32, P<0.002; FMD, 4.2±0.8% vs. 7.3±0.7%, in subjects with PRA < 0.5 and > 1.0 ngml-1hr-1respectively, P<0.0001). Change in salt intake over a two-week period did not significantly influence FMD. NG-monomethyl- L-arginine (L-NMMA) reduced fractional urinary sodium excretion whereas saline placebo was without an effect. The anti-natriuretic effect of L-NMMA was positively correlated with PRA (P<0.01, 3.4±7.0% % vs. 29.6±5.5% reduction in fractional sodium excretion in subjects with PRA < 0.5 and > 1.0 ngml-1hr-1respectively, P<0.01). These results suggest that, in predominantly asymptomatic subjects, renal sodium excretion is regulated by endotheliumderived or other peri-tubular source of NO. Reduced NO availability may underlie sodium retention and increased vascular risk associated with the low renin phenotype. Treatment with NO donors and/or enhancement of endogenous NO availability might be beneficial in subjects with low renin status. Further studies are required to explore the association of NO availability with sodium homeostasis in different groups (e.g. those with hypertension) and to test effects of interventions to modulate NO availability on sodium homeostasis and blood pressure in subjects with a low renin phenotype.
Supervisor: Chowienczyk, Philip Jan ; Ritter, James Michael Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.689172  DOI: Not available
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