uric acid and hypertension oussama hassan, md era-edtra fellow royal london hospital - barts health...
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Uric Acid and Hypertension
Oussama Hassan, MDERA-EDTRA Fellow
Royal London Hospital - Barts Health NHS Trust, London, UK
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Overview of uric acid
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History!
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Definition
• There is no universally accepted definition of hyperurecemia
• 7mg/dl is used as the cut off for the upper limit
• Above this value (6.8mg/dl) serum urate concentration exceeds the solubility limit
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Uric Acid Generation pathway
Humans lack uricase
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How is urate processed by the kidney
Four-component model for urate excretion :1- Filtration2- Almost complete reabsorption3- Secretion4- Postsecretoryreabsorption in a linear distribution along thelength of the proximal tubule
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How is urate processed in the kidney
• > 70% of hyperuricemia is due to under-excretion • The predominant mode of urate transport is
reabsorption• 5% to 10% of filtered urate is excreted in the urine• The proximal tubule has the capacity to dramatically
increase urate reabsorption => more than 99% of filtered urate can be reabsorbed even if the filtered load is increased fourfold by urate infusion
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Mechanism of hypertension
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Uric acid and BP in rats
OA: oxonic acid (uricase inhibitor)
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Uric acid and BP in rats
Allopurinol: XO inhibitor; Benziodarone: uricosuric agent
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Uric acid and BP in rats
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From animal models to humans
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Box and whisker plot
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Serum UA plotted against BP
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Postulated pathophysiology of
Hypertension in hyperuricemia
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A striking finding: juxtaglomerular renin content was increased and macula densa NOS1 expression was reduced => changes expected to result in both afferent and efferent arteriolar vasoconstriction => typical findings in many models of hypertension
OA: oxonic acid; AP: allopurinol
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Enalapril or L-Arginine Prevents Hypertension and Renal Disease in
Hyperuricemic Rats
OA: oxonic acidLS: low salt diet
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UA and RAS
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UA and Nitric oxide
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Correlation of UA and NO
Effect of uric acid on bovine aortic endothelial cells
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Uric acid stimulates VSMC proliferation and contributes to atherogenesis by increasing
PDGF
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Hyperuricemia and arteriolopathy
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Hyperuricemia and arteriolopathy
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Uric acid and Sodium
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Uric acid and Sodium
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Mechanism of HTN induced by UA
Increase Blood Pressure
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Proposed mechanism for Uric acid mediated HTN
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Uric acid and Hypertension
“People who are subject to this high blood pressure … frequently belong to gouty families, or have themselves suffered from the symptoms of this disease”
Frederick Mahomed. Lancet i:400, 1879
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Thank you