Abstract 628: Early Life Stress Exacerbates The Adrenergic Receptor Subtypes Mrna Expression In The Kidney

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Abstract

Maternal separation (MS) in rodents is a model of human chronic behavioral stress during early life. Previously we have shown that renal sympathetic system is sensitized in adult MS rats. Accordingly, we found that reduced glomerular filtration rate in intact MS rats was normalized after bilateral renal denervation (DnX). The aims of this study were to test the mRNA expression of adrenergic receptor (AR) subtypes in intact and DnX renal cortex and renal vessels. Also, to test the levels of mediators related to the alpha (1,4,5-trisphosphate, IP3) and beta (adenosine-3′,5′-cyclic monophosphate, cAMP) AR signaling pathways. MS was performed in WKY by separating approx half of the male pups from the dam 3 hr a day from days 2-14 of life. Renal tissue from 12 weeks old rats was harvested and snapped frozen. RT-PCR was performed using primers for ARs and IP3 receptor 1 and 2 and mRNA levels. cAMP was determined in renal cortex homogenates by ELISA. IP3 receptor mRNA expression was not different between MS and control rats in intact cortex, Dnx cortex or kidney vessels. cAMP was increased in intact renal cortex of MS rats compared to control (2.37±0.23 vs. 1.55±0.0.24 pmol/mg protein, respectively, p<0.05). Relative mRNA expression (2-ΔΔct) of α1a, α1b, α1d and α2b were not different in intact cortex from control and MS rats, while Dnx did not have any significant effect. However, α2c AR was increased in intact renal cortex from MS rats compared to control rats (4.5±1.2 vs. 1.8±0.3 2-ΔΔct, p<0.05). DnX significantly reduced α2c mRNA expression in renal cortex from MS and control rats (0.9±0.2 and 0.5±0.1 2-ΔΔct, p<0.05 vs. intact cortex). Relative mRNA expression of α1a, α1b, α1d, α2b and α2c were significantly increased in renal vessels tissue from MS rats compared to control rats (p<0.05).

We conclude that enhanced renal mRNA expression of ARs, especially α2c, may be a key mechanisms contributing to the lower glomerular filtration capacity in MS rats. Distinctive pharmacodynamic properties of α2c ARs suggest that they may be attractive targets for therapeutic intervention in case of exposition to early life stress.

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