ntrarenal distribution and regulation of Urotensin-II system in rats with chronic renal failure. I

Urotensin II (UII) was recently identifi ed in mammals as a potential modulator of
vascular tone by activating a specifi c receptor UT-R. However, little is known about
the functional relevance of this peptide. Since it was reported that plasma UII increased
in patients with chronic renal failure (CRF), our aim was to characterize the intrarenal
distribution and regulation of UII and UT-R in rats with normal renal function (Sham) or
CRF, achieved by 5/6 nephrectomy (5/6Nx). In vivo experiments were also undertaken in
anesthetized rats to evaluate the hemodynamic and renal effects of an intrarenal infusion
of UII (20 ng/kg/min). Immunohistochemistry and analysis of mRNA expression for UII
and UT-R using quantitative RT-PCR (Taqman) were performed on kidneys from Sham
and 5/6Nx rats. Intrarenal distribution of UII and UT-R in normal tissue is summarized
in the following table.
Glom PCT PST Henle's loop TAL DCT CD
U-II + - ++ + - +++ ++
UT-R - +++ - - +++ - -
Glom, glomerulus ; PCT-PST, proximal convoluted-straight tubule ; TAL, thick ascending lim ; DCT,
distal convoluted tubule ; CD, collecting duct
In 5/6Nx rats, UII-like immunoreactivity remained almost unaffected. A signifi cant
reduction of UT-R immunostaining in the inner stripe of outer medulla was confi rmed by
a four-fold decrease in UT-R mRNA in this area (P<0.05). In Sham rats (n=6), infusion
of UII decreased mean arterial pressure, renal blood fl ow and glomerular fi ltration rate
by 10, 17 and 11% (P<0.05), as well as diuresis and natriuresis by 30 and 40% (P<0.05).
Interestingly, these variables were not modifi ed by UII in 5/6Nx rats (n=6). In summary,
UT-R and UII-like immunoreactivity was present in normal and 5/6Nx rat kidneys, their
mutually exclusive localization further suggesting a paracrine way of action for UII.
Moreover, UII was shown to modulate in vivo hemodynamic and excretory functions of
the normal kidney. Interestingly, the blunted effects of UII in 5/6Nx rats, that could be
linked to a down-regulation of UT receptors, indicate that the functionality of this system
could be altered in rats with CRF.