MICROVASCULAR CONTROL OF JUXTAMEDULLARY NEPHRON FUNCTION

The long term aid of this proposal is to delineate and characterize the
mechanisms involved in maintaining blood flow and glomerular filtration
rate constant in the face of alterations in arterial pressure. Since renal
function is critically dependent on its microcirculation, understanding of
the mechanisms which contribute to microvascular control of renal function
at a single nephron level is of substantial interest. Emphasis will be
placed on establishing the role of the tubuloglomerular feedback mechanism
and the myogenic response in autoregulatory phenomena. Both mechanisms
have been previously suggested as important determinants of autoregulatory
efficacy; however, quantitative contributions of each mechanism to the
autoregulatory response have not been clearly established. Using a recently developed in vitro preparation that involves perfusion of
individual juxtamedullary nephrovascular units from rats with homologous
blood, the microvasculature of the kidney can be clearly visualized.
Videmoetric techniques will be utilized to evaluate the blood flow and
segmental vascular diameter changes which occur in response to alterations
in perfusion pressure. Micropuncture methodology will be used to measure
hydrostatic pressure in the vasculature, as well as to evaluate the
tubuloglomerular feedback-mediated changes in nephron function in response
to altering tubular fluid flow. Experiments will be performed to
characterize the autoregulatory response in vitro, to determine the
myogenic capability of the vasculature, and to determine the sensitivity of
the tubuloglomerular feedback system under these conditions. These
experiments will set the basis for studies designed to evaluate the
relative contributions of myogenic and tubuloglomeruler feedback mechanisms
to the autoregulatory response. Other studies will be performed to assess
whether or not there is any interaction between tubuloglomerular feedback
and myogenic influences on renal microvascular function. Finally, studies
will be performed to establish the dependency of autoregulation upon a
number of putative modulators of the tubuloglomerular feedback mechanism,
and to investigate the influence of suggested auto regulatory mediators
(histamine and adenosine) on the tubuloglomerular feedback loop. These
studies will help delineate the interrelationship between autoregulatory,
tubuloglomerular feedback, and myogenic systems involved in control of
renal microvascular function.