Chronic administration of Angiotensin II (Ang II) at low dose leads to progressive increases in arterial pressure and intrarenal accumulation of Ang II, which occurs by increased Ang II synthesis and Ang II receptor subtype 1 (AT1) mediated endocytosis. Since the internalized Ang II may have a functional role interacting with intracellular sites including nuclear Ang II binding sites reported in liver, adrenal cortex, cerebellum and smooth muscle but not in kidneys, the aims of this study were to determine if chronic infusion of Ang II changes the AT receptor densities in the rat renal cortex and if kidney cells have specific nuclear Ang II binding sites which densities may be altered by chronic administration of Ang II. Sprague Dawley rats were infused with Ang II at 70 ng/min via osmotic minipumps for 13 days and the tail cuff systolic blood pressures increased from 112 +/- 5 to 179 +/- 2 mmHg while the body weight gains decreased from 5.86 +/- 0.13 to 4.67 +/- 0.17 g/day, respectively, in control sham infused and Ang II infused rats (n = 17 and 13). On day 14, the kidneys were harvested and the renal cortexes homogenized to obtain crude membrane (CM), plasma membrane (PM) and nuclear fractions (NF) by differential centrifugation. A homologous competition assay between 125I-Sar1-Ile 8-AngII and Sar1-Leu8-AngII for binding sites in CM was used to determine the inhibitory concentration 50% (IC 50), Hill slopes, AT receptor affinities (Kd) and densities (Bmax). In addition, the total AT and AT1 binding densities in PM and NF were measured with a single point assay and alkaline phosphatase activity was used to determine purity/contamination of the fractions. The results indicated that; (a) the chronic infusion with Ang II did not alter the affinities or densities of its own receptors in the rat renal cortex, (b) AT 1 was the prevalent Ang II receptor subtype in the renal cortex, (c) AT 1 'like' binding sites were present in the nuclei of renal cells and (d) chronic administration of Ang II 'in vivo' did not alter Ang II binding sites in the nuclear fraction of the renal cortex / acase@tulane.edu
| Identifer | oai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_26546 |
| Date | January 2003 |
| Contributors | Licea Vargas, Hector (Author), Navar, L. Gabriel (Thesis advisor) |
| Publisher | Tulane University |
| Source Sets | Tulane University |
| Language | English |
| Detected Language | English |
| Rights | Access requires a license to the Dissertations and Theses (ProQuest) database., Copyright is in accordance with U.S. Copyright law |
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