Project: Research project

Project Details


The broad objective of this application is to define the effect of
atherosclerosis on the renal microcirculation and tubular function. Our
working hypothesis is that during the evolution of atherosclerosis,
renovascular endothelial dysfunction contributes to a reduction in
intra-renal perfusion and alterations in tubular dynamics, which may
eventuate in renal hemodynamic and functional damage, and may be
demonstrable even during hypercholesterolemia as blunted
microcirculatory and tubular responses to the endothelium-dependent
vasodilator and diuretic agent acetylcholine. Moreover, this renal
injury may be further aggravated with concurrent renal artery stenosis
or hypertension, but may regress upon return to a normal diet We
propose to use both electron-beam computed tomography (EBCT), a unique
scanner capable of quantifying the function of the regional renal
microcirculation and tubules in the in vivo, intact kidney, as well as
in vitro techniques in isolated renal microvessels. Our specific aims
are, hence, to determine in pigs regional renal perfusion and excretory
function before, during, and subsequent to reversal versus continuation
of hypercholesterolemia before and after administration of
acetylcholine, and in vitro in isolated renal microvessels.
Furthermore, to determine these parameters, with and without
hypercholesterolemia, in pigs with a concurrent super-imposed renal
artery stenosis, both in the stenosed kidney (exposed to low perfusion
pressure) and in the contra-lateral kidney (exposed to high arterial
pressure), and finally in normal pigs. The significance of this
proposal is that may greatly advance our recognition and understanding
of the mechanisms of renal damage during the evolution of
atherosclerosis, and contribute to developing strategies to protect the
kidney and cardiovascular system.

The applicant is an Assistant Professor in the Department of Physiology
at the Mayo Clinic, who plans to pursue a career as an independent
investigator. The applicant's immediate objective is to become a well
trained investigator capable of applying basic science techniques to
study renal and cardiac physiology and pathophysiology in both animal
and human models. The overall goal of the applicant's research is to
use high-resolution, noninvasive methods to acquire data describing the
in vivo cardiac and renal alterations and adaptive responses to
cardiovascular disease in general and evolving atherosclerosis in
particular, and furthermore, reliable data applicable for future
clinical diagnostic and therapeutical use.
Effective start/end date1/1/9712/31/00


  • Medicine(all)