GLP-1 mediated diuresis and natriuresis are blunted in heart failure and restored by selective afferent renal denervation

Figures

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  Fig. 1. ARNA response to intrapelvic injection of GLP-1. a Raw tracings of integrated and RSNA from Sham and HF rats. b Summary data for basal RSNA. c Raw tracings of integrated and ARNA from Sham and HF rats. The ARNA was recorded before and after intrapelvic injection of GLP-1 3 μM or capsaicin 100 μM to determine the peak level of ARNA (ARNAmax). d Summary data for ARNA. e Summary data for peak ARNA responses to GLP-1 expressed as an absolute value. f Summary data for peak ARNA responses to GLP-1 expressed a percentage of ARNAmax. g Summary data for peak ARNA responses to capsaicin. n = 6. *P < 0.05 vs. Sham

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  Fig. 2. GLP-1R expression in the renal pelvis. Real-time qRT-PCR (a) and western blot analysis (b) for GLP-1R in the renal pelvis of Sham and HF rats. n = 6. *P < 0.05 vs. Sham

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  Fig. 3. RSNA, MAP and HR responses to intravenous infusion of GLP-1. a Raw tracings of changes in RSNA, MAP and HR to intravenous (i.v.) infusion of GLP-1 in Sham and HF rats. b Summary data for the effect of GLP-1 on changes in RSNA, MAP and HR over 60 min. n = 5. *P < 0.05, **P < 0.01 vs. Sham

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  Fig. 4. Diuretic and natriuretic responses to intravenous infusion of GLP-1. Urine flow (a) and sodium excretion (b) in response to GLP-1 injection in Sham and HF rats. Cumulative values of urine flow (c) and sodium excretion (d) in response to GLP-1 injection in Sham and HF rats. n = 10. *P < 0.05, **P < 0.01 vs. Sham

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  Fig. 5. Effects of T-RDN or A-RDN on diuretic and natriuretic responses to intravenous infusion of GLP-1. Urine flow (a, c) and sodium excretion (b, d) in response to GLP-1 injection in Sham (a, b) and HF (c, d) rats with or without T-RDN and A-RDN. n = 6–10. *P < 0.05, **P < 0.01 between rats with and without T-RDN. #P < 0.05, ##P < 0.01 between rats with and without A-RDN

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  Fig. 6. Validation of A-RDN by western blot analysis. Relative CGRP and TH protein expression in the renal pelvis of Sham and HF rats with or without A-RDN. n = 6. ##P < 0.01 between rats with and without A-RDN

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  Fig. 7. Effects of T-RDN or A-RDN on MAP and HR responses to intravenous infusion of GLP-1. MAP and HR changes in response to GLP-1 injection in Sham (a, b) and HF (c, d) rats with or without T-RDN and A-RDN. n = 5–7. *P < 0.05, **P < 0.01 between rats with and without T-RDN. #P < 0.05, ##P < 0.01 between rats with and without A-RDN

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  Fig. 8. Proposed model for neural mechanisms in regulating GLP-1 mediated diuresis and natriuresis in HF. GLP-1 activates afferent renal nerve via GLP-1R expressed in the renal pelvis to increase efferent renal nerve activity that regulate diuresis and natriuresis in an inhibitory manner. In HF condition, there is an excessive activation of afferent renal nerve due to an overexpression of GLP-1R in the renal pelvis resulting in an excessive activation of efferent renal nerve thereby suppressing diuresis and natriuresis. Either A-RDN or T-RDN inhibits the activation of neural circuitry utilizing the renal nerves to restore GLP-1 mediated diuresis and natriuresis