REGULATION OF INDIVIDUAL NEPHRON FILTRATION RATES

The long-term objective is to increase understanding of the regulation of
nephron function by exploiting the unique structure of avian kidneys, the
highly specialized structure of kidneys of desert rodents, and the
specialized transport properties of mammalian and avian nephrons. Avian
kidneys have nephrons resembling reptilian nephrons with very simple
glomeruli (single capillary loop) that function independently of each, do
not contribute directly to the concentrating mechanism, and can cease
filtering altogether under some circumstances; nephrons resembling
mammalian nephrons that function together in the concentrating mechanism,
do not normally cease filtering, but may alter their filtration rates; and
both arterial and portal venous blood supplies One strain of chickens has
nephrogenic diabetes insipidus. Kidneys of desert rodents have
juxtamedullary nephrons several times larger than superficial cortical
nephrons and a very long papilla. This structural heterogeneity of
nephrons is intermediate between the structural heterogeneity of nephrons
in avian kidneys and laboratory rat kidneys. The primary goals involve
studies of: 1) glomerular structure and function, including quantitative
ultrastructure and filtration will pressures in avian kidneys; and 2)
medullary function and concentrating mechanism, including amino acid
transport by juxtamedullary mammalian nephrons, the role of amino acids in
mammalian medullary function, and concentrating defect(s) in birds with
genetic nephrogenic diabetes inipidus. Computer-assisted quantitative
ultrastructural analysis of the filtration barrier and the area available
for filtration will be used to examine simple avian glomerulus. In vivo
micropuncture pressure measurements will help define avian glomerular
filtration dynamics in relation to structure in varying diuretic states.
In vivo micropuncture and continuous microinfusion, in vitro
microperfusion, and amino acid analyses of micropuncture samples and kidney
slice extracts will be used to further define amino acid reabsorption
distal to the tips of Henle's lops of juxtamedullary nephrons, recycling of
amino acids for cellular osmotic and volume regulation during urine
concentration in laboratory rats and desert rodents. In vivo clearance
determinations and portal infusions and in vitro perfusions of isolated
avian collecting ducts and determinations of enzyme activities in these
collecting ducts will be used to define the renal defect(s) in chickens
with nephrogenic diabetes insipidus.