Angiotensin II has been recently shown to be a potent regulator of transport in the rat proximal convoluted tubule (PCT). The overall objective of this proposal is to establish whether transport regulation by angiotensin II contributes to the renal physiologic response when dietary NaCl changes. The working hypothesis is: Under normal conditions, the quantity of dietary NaCl sensitively modulates renin activity and angiotensin II concentration. Angiotensin II, by virtue of its powerful regulation of transport in the S, segment of the PCT, controls the quantity of NaCl delivered out of the PCT. Angiotensin II would thus an important determinant by which the kidney adjusts NaCl excretion to match intake. Established in vivo and in vitro techniques in rats will be used. In response to an alteration in dietary NaCl intake in normal, euvolemic Munich-Wistar rats, the specific aims of this project are: a) Using in vivo microperfusion, to examine the magnitude of angiotensin II-mediated changes in S, and S, PCT bicarbonate, chloride and water transport. b) Using in vivo free-flow micropuncture and clearance techniques, to establish the magnitude by which altered angiotensin II activity, which predominantly affects NaHCO, and NaCl reabsorption in the S1 PCT, changes NaCl delivery out of the S2 PCT, and the ii subsequent impact of these proximal transport alterations on distal NaCl delivery and urinary NaCl excretion. c) Using in vitro microdissection and radioligand-binding techniques, to examine cellular mechanisms which might participate in the S1 PCT cellular response to dietary-induced change in endogenous angiotensin II by assessing whether altered angiotensin II receptor density on the S1 epithelial cell occurs due to homologous sensitization.
| Wong, K R; Berry, C A; Cogan, M G (1996) Alpha 1-adrenergic control of chloride transport in the rat S1 proximal tubule. Am J Physiol 270:F1049-56 |
| Wong, K R; Berry, C A; Cogan, M G (1995) Chloride transport in the rat S1 proximal tubule. Am J Physiol 268:F723-9 |
| Wong, K R; Berry, C A; Cogan, M G (1995) Flow dependence of chloride transport in rat S1 proximal tubules. Am J Physiol 269:F870-5 |
| Cogan, M G; Liu, F Y; Wong, P C et al. (1991) Comparison of inhibitory potency by nonpeptide angiotensin II receptor antagonists PD123177 and DuP 753 on proximal nephron and renal transport. J Pharmacol Exp Ther 259:687-91 |
