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

    loading  Checking for direct PDF access through Ovid


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.

Related Topics

    loading  Loading Related Articles