Oussama Hassan MD ERAEDTRA Fellow Royal London Hospital Barts Health NHS Trust London UK Overview of uric acid History Definition There is no universally accepted definition of ID: 927993
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Slide1
Uric Acid and Hypertension
Oussama Hassan, MD
ERA-EDTRA Fellow
Royal London Hospital -
Barts
Health NHS Trust,
London,
UK
Slide2Overview of uric acid
Slide3History!
Slide4Slide5Slide6Definition
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
Slide7Uric Acid Generation pathway
Humans lack
uricase
Slide8Slide9How is
urate
processed by the kidney
Four-component model for
urate
excretion :
1- Filtration
2- Almost complete reabsorption
3- Secretion4- Postsecretory
reabsorption in a linear distribution along the
length of the proximal tubule
Slide10How 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 urineThe 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
Slide11Mechanism of hypertension
Slide12Slide13Uric acid and BP in rats
OA:
oxonic
acid (
uricase
inhibitor)
Slide14Uric acid and BP in rats
Allopurinol
: XO inhibitor;
Benziodarone
:
uricosuric
agent
Slide15Uric acid and BP in rats
Slide16From animal models to humans
Slide17Slide18Slide19Slide20Box and whisker plot
Slide21Serum UA plotted against BP
Slide22Postulated pathophysiology of Hypertension in
hyperuricemia
Slide23A 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
Slide24Enalapril
or L-
Arginine
Prevents Hypertension and Renal Disease in
Hyperuricemic
Rats
OA:
oxonic
acid
LS: low salt diet
Slide25UA and RAS
Slide26UA and Nitric oxide
Slide27Correlation of UA and NO
Effect of uric acid on bovine aortic endothelial cells
Slide28Uric acid stimulates VSMC proliferation and contributes to
atherogenesis
by increasing PDGF
Slide29Hyperuricemia and
arteriolopathy
Slide30Hyperuricemia and
arteriolopathy
Slide31Uric acid and Sodium
Slide32Uric acid and Sodium
Slide33Slide34Mechanism of HTN induced by UA
Increase Blood
Pressure
Slide35Proposed mechanism for Uric acid mediated HTN
Slide36Uric 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
Slide37Thank you