Abstract 3538: Suppressed Afferent Renal Nerve Activity Contributing to Dahl Salt Sensitive Hypertension: Role of TRPV1
We have previously shown that activation of transient receptor potential vanilloid type 1 (TRPV1) channels in the renal pelvis leads to increased afferent renal nerve activity (ARNA) and diuresis and natriuresis, indicating that TRPV1 in the renal pelvis plays a key role in the regulation of sodium and water homeostasis and blood pressure. This study tests the hypothesis that TRPV1-mediated increases in ARNA and the release of sensory neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP), in the renal pelvis are impaired in Dahl salt sensitive (DS) rats fed a high salt diet. Male DS and Dahl salt-resistant (DR) rats at 5 week age were given high salt (HS) or low salt (LS) diets for 3 weeks. Mean arterial pressure (MAP, mmHg) was increased in DS-HS (150 ± 8, p<0.05) compared to DS-LS (112±10), DR-HS (113±6) and DR-LS (110±10). Perfusion of capsaicin (CAP, 10−6M), a selective TRPV1 agonist, into the left renal pelvis caused increases in ARNA in all groups, and CAP-induced increases in ARNA was smaller in DS-HS (168± 22%, p<0.05) compared to DS-LS (209±19%), DR-HS (203±20%), and DR-LS (226±25%) rats. Suppressed ARNA induced by CAP observed in DS-HS rats was not due to higher MAP in this group given that CAP-induced increases in ARNA was not suppressed in DOCA salt hypertensive rats (224±17%) that had comparable MAP as that of DS-HS rats. CAP-induced release of SP and CGRP (pg/g/min) from the renal pelvis was smaller in DS-HS (SP 1.2±0.6, CGRP 25.6±4.7, p<0.05) compared to DS-LS (SP 3.1±1.1, CGRP 37.8±11.2), DR-HS (SP 2.3±1.1, CGRP 35.3±7.1), DR-LS (SP 2.3±1.4, CGRP 41.8±11.3), and DOCA-salt rats (SP 2.5±1.1, CGRP 38.4±9.1). Western blot showed that TRPV1 expression in the renal pelvis was decreased in DS-HS compared to DS-LS, DR-HS, DR-LS and DOCA salt rats (p<0.05), while expression of neurokinin 1 (NK1) receptors in the renal pelvis unchanged in all groups. Our data show that TRPV1-mediated increases in ARNA and the release of SP and CGRP in the renal pelvis are impaired in DS rats fed a HS but not NS diet, which may be due to impaired TRPV1 expression in response to HS intake in these rats. The impairment in TRPV1 function and regulation in DS rats fed a HS diet is not the result of elevated blood pressure but likely contributes to increased salt sensitivity in DS rats.