Our purpose is to investigate prostacyclin(PGI2)-angiotensin II (AII) interactions in isolated glomeruli which may determine the centrifugal redistribution of cortical blood flow when nephrogenesis has been completed in the developing mammalian kidney. Changes in prostaglandin (PG) synthesis, renin release (RR) and AII formation by glomeruli isolated from the juxtamedullary (JM) or superficial (SC) renal cortex of neonatal and adult dog kidneys will be measured in vitro and results compared developmentally with changes in blood volume (BV) and extracellular fluid volume (ECFV), with circulating levels of PG, AII and arginine vasopressin (AVP), with plasma renin activity, and with urinary excretion of PGs and AVP. Moreover, developmental differences in release of vasoactive substances from glomeruli will be studied in vitro when the concentrations of circulating vasoactive substances such as PGI2, PGE2, AII, AVP and catecholamines in the incubation medium are similar to those measured in arterial plasma of neonates and adults. The influence of chronic differences in ECFV in vivo on glomerular PG synthesis, RR and AII formation in the JM or SC renal cortex will be studied in vitro in developing and mature kidneys. Finally, the differential effects of PGI2 and AII in vivo will be assessed in isolated glomeruli harvested from developing and adult kidneys subjected to chronic selective PG or AII inhibition studies and to acute changes in BV. Radioimmunoassay and radiochromatography techniques after high performance liquid chromatography or thin layer chromatography separation will be used to measure metabolites of PGI2, PGE2, PGF2Alpha, thromboxane B2 renin, AI and AII and AVP in plasma, urine or incubation medium in which glomeruli have been incubated with unlabeled or radiolabeled [14C] arachidonic acid. Glomerular filtration rate during mammalian renal development increases pari passu with increments in renal blood flow. The physiologic adaptation of the premature human infant to extrauterine life is often complicated by therapeutic modalities, by pharmacologic agents such as diuretics, pressor drugs and indomethacin, and by diseases which alter both renal function as well as PG-AII metabolism. The long-term objective of this project is to identify physiologic mechanisms that effect changes in renal function during normal development, but when perturbed in the neonatal period have pathophysiologic consequences to impair renal glomerular and tubular functions and to increase morbidity among high-risk infants.
| Seikaly, M G; Arant Jr, B S; Seney Jr, F D (1990) Endogenous angiotensin concentrations in specific intrarenal fluid compartments of the rat. J Clin Invest 86:1352-7 |
