The effect of ARB in diabetic nephropathy

The main goal in the treatment of diabetic

nephropathy: control of the glycaemic status and
aggressive antihypertensive therapy (decreasing
the blood pressure (BP) below 130/85 mmHg),
primarily with RAAS-blocking agents.
It was demonstrated recently that angiotensin II
receptor blockers (ARBs) have a slowing effect
on the progression of diabetic nephropathy
(RENAAL and IDNT trials) or on the development
of proteinuria (IRMA) in type 2 diabetes.

 Angiotensin receptor blockers (ARBs)

represent a new class of
antihypertensive drugs that block the
RAAS. They selectively block the AT1
receptor and in this way inhibit the
vasoconstrictive and tissuedamaging effects of Ang II in
diabetes, including growth,
inflammation and thrombosis.

 RENAAL Study Losartan reduced the

relative risk of the primary composite endpoint as compared with the placebo group
by 16% (P < 0.02), reduced the incidence
of doubling of serum creatinine by 25% (P
< 0.006) and reduced ESRD by 28% (P <
0.02). The proteinuria was also
significantly decreased.
The optimal dose of losartan is 100 mg
daily for renoprotection and blood pressure
reduction in such patients.

 IDNT Study Irbesartan displayed an even more

significant RR reduction vs amlodipine, by 23% of
the composite end-point (P < 0.006), and by 37%
of the doubling of serum creatinine (P < 0.001). In
this comparison, the incidence of ESRD was on the
borderline of significance, vs both the placebo and
amlodipine. The ARB treatment significantly
decreased the proteinuria.
Irbesartan at a dosage of 300 mg once daily was
superior in lowering albuminuria as compared with
150 mg irbesartan daily.

The effect of ARB in stress related disorders

Peripheral administration of the AT1 antagonist
candesartan blocks brain AT1 receptors and
prevents the hormonal and sympathoadrenal
response to isolation stress.
Peripheral administration of a selective, potent,
insurmountable AT1 antagonist such as
candesartan, when administered for 2 weeks,
significantly decreased AT1 receptor binding, not
only inperipheral tissues and circumventricular
organs, but also in the hypothalamic
paraventricular nucleus and in the nucleus of the
solitary tract
Our results demonstrated that simultaneous

 To establish whether or not AT1 receptor

blockade couldbe of therapeutic benefit,
there was a study of the effects of
candesartan on the development of stressinduced disorders.
Candesartan dramatically decreased the
number of ulcerations produced by coldrestraint stress,protecting the gastric mucosa
from stress-induced injury, decreased the
formation of the stress-induced
adrenomedullary catecholamine, increased

 Stress increased the expression of the pro

inflammatory cytokine TNF-a, ICAM-1
damaging endothelial cells, production of
gastric lesions
Ang II promotes tissue inflammation,
enhancing neutrophil infiltration through AT1
receptor stimulation, increased expression of
TNF-a, ICAM-1.
Pretreatment with the AT1 antagonist
decreased the stress-induced overexpression
of TNF-a and ICAM-1 overexpression and the
neutrophil infiltration in the gastric mucosa
indicating that the anti-inflammatory effects