RENAL MEDULLARY NITRIC OXIDE AND BLOOD PRESSURE

Project: Research project

Project Details

Description

Previous data from our laboratory demonstrated the importance of
renal medullary. NOS in the short- and long-term control of renal
function and arterial pressure. The role of the individual NOS
isoforms in the control of renal function and arterial pressure is
not clear. Recent work from our laboratory indicates that
inducible NOS (INOS) is present in high levels in the renal
medulla of normal rats and chronic systemic iNOS inhibition leads
to an elevation of arterial pressure. This proposal will address the
hypothesis that renal medullary iNOS is differentially expressed in
different cell types in the renal medulla of normal rates and
influences sodium and water excretion by direct effects at the level
of the colocynth duct.

Experiments will be performed in the first half of this proposal to
determine the acute and chronic fluid and electrolyte balance and
blood pressure effects of selective inhibition of renal medullary
iNOS. These experiments will be performed using techniques
unique to our laboratory (implanted optical fibers for laser-
Doppler flometery and selective infusion directly into the renal
medullary interstitial space) as renal medullar iNOS is inhibited
with selective enzyme inhibitors. Confirmation of inhibition will
be determined by in vitro measures of NOS enzyme activity in
tissues obtained from the treated animals. These experiments will
demonstrate the importance of iNOS in the regulation of sodium
and water balance and blood pressure.

The experiments in the second half of the proposal will focus on
the distribution and functional importance of iNOS in renal tubular
and vascular segments as sodium intake is changed. comparison of
mRNA levels, immunoreactive protein levels, and calcium-
dependent and -independent NOS enzymatic activity will initially
be performed on whole tissue obtained from rats maintained on a
low, normal, or high sodium intake. Quantitative RT-PCR
measurements of mRNA for iNOS will then be used to determine
the location and relative quantity of iNOS message in
microdissected renal medullary tubular and/or vascular segments.
Finally, the relationship between sodium intake and blood pressure
in rats chronically administered with the selective iNOS inhibitors
will be determined to in order to draw a functional correlate with
the observed changes in iNOS in renal medullary structures.
StatusNot started