MICROVASCULAR CONTROL OF JUXTAMEDULLARY NEPHRON FUNCTION

The purpose of this project is to delineate the mechanisms
involved in regulating blood flow to juxtamedullary nephrons of
the rat kidney. Emphasis is placed on characterization of the
ability of the vasculature to maintain blood flow and glomerular
filtration rate constant in the face of alterations in perfusion
pressure, including evaluation of the role of several mechanisms
which may be involved in this autoregulatory response. (Primary
candidates include the tubuloglomerular feedback and myogenic
mechanisms.) Also, the renal microvascular responses to
important vasoactive agents will be evaluated. Experiments will be performed using an in vitro preparation which
involves perfusion with homologous blood of juxtamedullary
nephrons from the rat kidney. This experimental setting allows
visualization of the renal arterial and arteriolar units.
Videometric techniques will be utilized to evaluate the blood flow
and segmental vascular diameter responses to changes in
perfusion pressure or alterations in tubular fluid flow to the distal
nephron; micropuncture techniques will be used to measure
hydrostatic pressure in the vasculature, collect tubular fluid, and
perfuse tubules from proximal tubular sites. Experiments will be
performed to characterize the autoregulatory response in vitro, to
determine the myogenic capability of the renal vasculature, and
to determine the sensitivity of the tubuloglomerular feedback
system under these conditions. These experiments will provide
the basis for studies designed to evaluate the relative
contributions of myogenic and tubuloglomerular feedback
mechanisms to the autoregulatory response. In addition, studies
will be performed to establish the dependency of autoregulation
upon a number of putative modulators of the tubuloglomerular
feedback system, and to investigate the influence of suggested
autoregulatory mediators on the tubuloglomerular feedback loop.
These studies will help delineate the interrelationships between
autoregulatory, tubuloglomerular feedback, myogenic, and
humoral influences on renal microvascular function.