Effect of Losartan or Eprosartan on Fructose Hyperuricemia
Status:
Completed
Trial end date:
2010-01-01
Target enrollment:
Participant gender:
Summary
Hyperuricemia is seen in about 20% of adults in the general population, Chronic
hyperuricemia, frequently manifesting as the gout, is a well-known risk factor of joint
damage but has been also linked to a variety of other pathologies mostly affecting the
cardiovascular system. The close relation between high uric acid concentration and increased
risk of cardiovascular disease has been reported for more than a century. Furthermore, many
studies reported a strong association between hyperuricemia, arterial hypertension, obesity
and cardiovascular diseases even in an absence of typical clinical manifestations of gout.
Several studies showed that the prevalence of hyperuricemia in patients with hypertension is
much higher than in the general population and may worsen after the onset of antihypertensive
treatment. That may indicate that hyperuricemia may be also caused by antihypertensive drugs.
In contrast to diuretics and nonselective beta blockers the agents that block the
renin-angiotensin-aldosterone system have had a neutral effect on serum uric acid. Several
clinical studies showed that losartan in contrast to other AT1-receptor agonists, may have
specific uricosuric properties and thereby can lower uric acid concentration. It has been
speculated that uricosuric effect could make losartan particularly useful for the treatment
of arterial hypertension associated with hyperuricemia and metabolic syndrome.
The uricosuric effect of losartan is most likely due to overlapping two different mechanisms
regulating the excretion of uric acid. Losartan may increase uric acid tubular secretion in
the same way as other inhibitors of the renin-angiotensin-aldosterone system, but in addition
it may specifically inhibit post-secretory resorption of uric acid in the proximal tubule.
The effect may be due to a specific structure of the losartan molecule. The urateanion
transporter is a monoammonium selective transporter, and the losartan molecule is mainly a
monoanion at normal pH range (as opposed to dianion e.g. eprosartan) and therefore is a good
substrate for the exchanger. However, this concept remains speculative since, e.g. irbesartan
which is also a monoanion has no consistent uricosuric effect.
Fructose, in contrast to other carbohydrates causes an increase of serum uric acid
concentration, which may facilitate the development of the metabolic syndrome.