Effects of increased circulating angiotensin II (AII) on fluid exchange and binding of All in the brain

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Previous studies have shown that elevated levels of circulating angiotensin II (AII) can influence the binding capacity of this peptide for its receptors in peripheral tissues, but the effect of increased circulating levels of AII on its receptors in the brain has not been well-defined. In the present study, the effect of chronic subcutaneous infusions of AII on: (1) the binding of AII to neuronal membranes from the diencephalon (hypothalamus, thalamus and septum) (HTS) of the brain; (b) water intake and urine output, (c) blood pressure, and (d) their interrelationships was evaluated in rats. Significant increases in daily water intake and urine output accompanied chronic infusions of AII at a rate of 125 ng/kg/min. Both blood pressure and the concentration of aldosterone in plasma were also elevated in these rats. The acute dipsogenic response to either central (10 ng) or peripheral ( 100 μg/kg, SC) administration of All was also tested both in controls and in rats receiving chronic infusions of AII at a rate of either 40 or 125 ng/kg/min, and no differences were observed. Analysis of the HTS region of the brain revealed a significant increase in the specific binding of AII in AII-infused rats compared to controls. Scatchard analysis of the specific binding of AII to its receptors in the HTS of rats treated with 40 ng AII/kg/min for 6 days revealed a significant increase in the number of binding sites for AII compared to controls (B max 12.13 vs. 8.79 fmol/mg protein), but no change in binding affinity (K d). Significant correlations were found between the specific binding of All in the HTS and daily water intake ( r = 0.94) as well as urine output ( r = 0.69). Thus, the increase in the specific binding of AII in the HTS may be the result of a direct effect of the increased concentrations of either AII or aldosterone, or both in plasma. Additional studies will be needed to clarify this.