Uric Acid and Hypertension

Oussama Hassan, MDERA-EDTRA Fellow

Royal London Hospital - Barts Health NHS Trust, London, UK

Overview of uric acid

History!

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

Uric Acid Generation pathway

Humans lack uricase

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

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

Mechanism of hypertension

Uric acid and BP in rats

OA: oxonic acid (uricase inhibitor)

Uric acid and BP in rats

Allopurinol: XO inhibitor; Benziodarone: uricosuric agent

Uric acid and BP in rats

From animal models to humans

Box and whisker plot

Serum UA plotted against BP

Postulated pathophysiology of

Hypertension in hyperuricemia

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

Enalapril or L-Arginine Prevents Hypertension and Renal Disease in

Hyperuricemic Rats

OA: oxonic acidLS: low salt diet

UA and RAS

UA and Nitric oxide

Correlation of UA and NO

Effect of uric acid on bovine aortic endothelial cells

Uric acid stimulates VSMC proliferation and contributes to atherogenesis by increasing

PDGF

Hyperuricemia and arteriolopathy

Hyperuricemia and arteriolopathy

Uric acid and Sodium

Uric acid and Sodium

Mechanism of HTN induced by UA

Increase Blood Pressure

Proposed mechanism for Uric acid mediated HTN

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

Thank you