Aldosterone Sensitizes Connecting Tubule Glomerular Feedback via the Aldosterone Receptor GPR30.

Aldosterone Sensitizes Connecting Tubule Glomerular Feedback via the Aldosterone Receptor GPR30. Am J Physiol Renal Physiol. 2014 Jun 25; Authors: Ren Y, D'Ambrosio MA, Garvin JL, Leung P, Kutskill K, Wang H, Peterson EL, Carretero OA Abstract Increasing Na delivery to epithelial Na channels (ENaC) in the connecting tubule (CNT) dilates the afferent arteriole (Af-Art), a process we call connecting tubule glomerular feedback (CTGF). We hypothesize that aldosterone sensitizes CTGF via a nongenomic mechanism that stimulates CNT ENaC via the aldosterone receptor GPR30. 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. During the control period, the concentration of NaCl that elicited a half-maximal response (EC50) was 37.0±2.0 mmol/L; addition of aldosterone 10-8 mol/L to the CNT lumen caused a left-shift (decrease) in EC50 to 19.3±1.3 mmol/L (P=0.001 vs. Control; n=6). Neither the transcription inhibitor actinomycin D (control EC50=34.7±1.9 mmol/L; aldosterone+actinomycin D EC50=22.6±1.6 mmol/L; n=6; P < 0.001) nor the translation inhibitor cycloheximide (control EC50=32.4±4.3 mmol/L; aldosterone+cycloheximide EC50=17.4±3.3 mmol/L; n=6; P < 0.001) prevented the effect of aldosterone. The aldosterone antagonist eplerenone prevented the sensitization of CTGF by aldosterone (control EC50=33.2±1.7 mmol/L; aldos...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research