Abstract P264: Ghrelin-Induced Sodium Reabsorption is Mediated by PKA and a Microtubulin-Dependent Network In Rats

Abstract

Previous studies have shown that intrarenal ghrelin infusion activates ghrelin receptors in the collecting duct to increase αE Na C-dependent sodium (Na + ) reabsorption in vivo , but the underlying mechanisms are unknown. 72h following uninephrectomy, 12-week-old female Sprague-Dawley rats received the following renal interstitial (RI) infusions for 1h after a 1h control period in which they received RI infusions of vehicle (5% dextrose in water, D 5 W): (1) vehicle (N=7), (2) ghrelin (3 μg/min, N=6), (3) ghrelin + PI3K inhibitor, LY-294002 (0.1 μg/kg/min, N=6), (4) LY-294002 alone (N=4), (5) ghrelin + PKA inhibitor, Rp-cAMPS (10 μg/kg/min, N=7), (6) Rp-cAMPs alone (N=5), (7) ghrelin + microtubule polymerization inhibitor nocodazole (3 μg/kg/min, N=7), (8) nocodazole alone (N=6), (9) ghrelin + actin polymerization inhibitor, cytochalasin D (0.3 μg/kg/min, N=6), and (10) cytochalasin D alone (N=6). Compared to baseline, RI ghrelin significantly decreased U Na V to 52.2 ± 9.9% (P<0.001), but this effect was abolished during concomitant PKA and microtubulin inhibition (128.6 ± 15.9% and 123.5 ± 12.2%, respectively, both P<0.01 from ghrelin alone). Ghrelin-induced antinatriuresis persisted in the presence of PI3K and actin inhibition (62.2 ± 4% and 59.7 ± 10.8% respectively, both P<0.01 from baseline and P=NS from ghrelin alone). RI infusion of inhibitors alone had no effect on U Na V compared to vehicle and mean arterial pressures did not change following any RI infusion. Taken together, these studies highlight the importance of PKA and microtubulin polymerization in αE Na C-mediated Na + reabsorption.