Abstract 552: Aldosterone Enhances Connecting Tubule Glomerular Feedback (CTGF)

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Abstract

Increasing Na delivery to the connecting tubule (CNT) stimulates epithelial Na channels (ENaC) and dilates the afferent arteriole (Af-Art), a process we call connecting tubule glomerular feedback (CTGF). We hypothesize that aldosterone (aldo) enhances CTGF via a nongenomic mechanism that stimulates CNT ENaC via GPR30 and/or mineralocorticoid receptors (MR). Rabbit Af-Arts and their adherent CNTs were microdissected and simultaneously perfused. Two consecutive CTGF curves were elicited by increasing luminal NaCl in the CNT. Addition of aldo 10-8 M to the CNT potentiated CTGF, seen as a left-shift in the concentration of NaCl that elicited a half-maximal response (EC50), see Figure. The MR blocker eplerenone (10-5 M) prevented the enhancement of CTGF by aldo (control EC50 = 32.4 ± 2.3 mM; aldo + eplerenone EC50 = 35.4 ± 1.7 mM; n = 7). Neither the transcription inhibitor actinomycin D (5x10-6M) nor the translation inhibitor cycloheximide (10-5M) prevented the effect of aldo (control EC50 = 33.0 ± 2.0 mM; aldo + actinomycin D EC50 = 15.4 ± 1.5 mM; n = 6; P < 0.001, control EC50 = 33.2 ± 2.4 mM; aldo + cycloheximide EC50 = 11.2 ± 1.3 mM; n = 6; P < 0.001). We conclude that aldo in the lumen of the CNT enhances CTGF via a nongenomic effect possibly involving MR and/or GPR30 receptors. Enhanced CTGF induced by aldosterone may contribute to renal damage by causing increases in Af-Art dilation and glomerular capillary pressure (glomerular barotrauma).

Figure. Control CTGF (○) seen as dilation of norepinephrine-preconstricted Af-Arts induced by increasing NaCl in the CNT. Aldo 10-8M (•) enhanced CTGF (n = 6; *P < 0.05; ** P < 0.01; *** P < 0.001; vs. control). Vertical dashed lines indicate EC50.

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