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      Potassium Depletion Stimulates mRNA Expression of Proximal Tubule AT 1 Angiotensin II Receptors



      S. Karger AG

      Kidney, Angiotensin, Receptors, Hypokalemia

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          Dietary potassium (K<sup>+</sup>) deficiency is associated with blood pressure elevation and impaired urinary sodium excretion. Since angiotensin II is a potent stimulator of tubular sodium transport, we studied the effect of low [K<sup>+</sup>] on expression of kidney AT<sub>1</sub> angiotensin receptors. In rabbits fed a K<sup>+</sup>-deficient diet for 14 days, plasma [K<sup>+</sup>] was significantly reduced compared to rabbits fed a standard diet (control: 4.06 ± 0.12 vs. K<sup>+</sup>-deficient: 2.66 ± 0.19 mmol/l; p < 0.001; n = 6–9). By Northern hybridization or RNase protection assays, dietary K<sup>+</sup> deficiency caused an increase in mRNA expression for AT<sub>1</sub> receptors in kidney cortex (43.5 ± 12.9% increase vs. control; p < 0.04; n = 8), and in proximal tubule segments in suspension (76.4 ± 28.8% increase vs. control; p < 0.005; n = 6). K<sup>+</sup> deficiency had no effect on AT<sub>1</sub> receptor mRNA expression in liver, or on mRNA expression of β-actin in kidney cortex, proximal tubule suspensions, or liver. To determine if low extracellular [K<sup>+</sup>] might directly modulate AT<sub>1</sub> receptor mRNA expression, primary cultures of rabbit proximal tubule cells were incubated for 1, 3, 6 or 24 h in media with or without 5 mmol/l K<sup>+</sup>. Incubation of cells in 0 mmol/l K<sup>+</sup> caused a 99.2 ± 32.9% increase in AT<sub>1</sub> receptor mRNA expression at 3 h (p < 0.001; n = 14), returning to control levels by 24 h. Incubation of proximal tubule cells in 0 mmol/l K<sup>+</sup> also caused a significant increase in basolateral membrane specific binding of [<sup>125</sup>I]-angiotensin II (p < 0.05; n = 4). These results indicate that dietary K<sup>+</sup> deficiency and low extracellular [K<sup>+</sup>] stimulate expression of kidney AT<sub>1</sub> angiotensin II receptors. Increased AT<sub>1</sub> receptor mRNA and protein expression in proximal tubule may promote enhanced sodium reabsorption in K<sup>+</sup> deficiency.

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          Most cited references 3

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          Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.

          A new method of total RNA isolation by a single extraction with an acid guanidinium thiocyanate-phenol-chloroform mixture is described. The method provides a pure preparation of undegraded RNA in high yield and can be completed within 4 h. It is particularly useful for processing large numbers of samples and for isolation of RNA from minute quantities of cells or tissue samples.
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            Identification of two subtypes in the rat type I angiotensin II receptor.

             T Inagami,  N Iwai (1992)
            A rat adrenal cDNA library was screened by colony hybridization using a rat cDNA fragment of type I angiotensin II receptor (AT1A) previously isolated from the kidney. Two cDNA clones were identified, designated as AT1B, to have a nucleotide sequence highly homologous to and yet distinct from AT1A. The amino acid sequence of AT1B consists of 359 amino acid residues and has 96% identity with AT1A. No conspicuous difference in the ligand binding characteristics was observed between AT1A and AT1B. The mRNA for AT1B was expressed in many tissues as is the case with AT1A, and most abundantly expressed in the adrenal glands in the Sprague-Dawley rats. The existence of two subtypes in the rat type I angiotensin II receptor might explain the diverse actions of angiotensin II in various tissues.
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              Different effects of chronic K+ depletion on forebrain and peripheral angiotensin II receptors in young rats


                Author and article information

                S. Karger AG
                January 1998
                19 December 1997
                : 78
                : 1
                : 73-81
                Departments of Medicine and Physiology, University of Ottawa, andOttawa General Hospital, Ottawa, Ont., Canada
                44885 Nephron 1998;78:73–81
                © 1998 S. Karger AG, Basel

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                Page count
                Figures: 5, Tables: 1, References: 44, Pages: 9
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                Original Paper

                Cardiovascular Medicine, Nephrology

                Hypokalemia, Receptors, Angiotensin, Kidney


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