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Capsaicin‐mediated selective afferent renal nerve denervation: effects on intrarenal responses to bradykinin and adenosine in conscious Sprague‐Dawley rats (687.2)
Author(s) -
Wainford Richard
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.687.2
Subject(s) - capsaicin , medicine , endocrinology , denervation , adenosine , natriuresis , chemistry , guanabenz , bradykinin , kidney , receptor , agonist
Aim: It has been reported that capsaicin evokes selective denervation of the renal afferent nerves in rats as confirmed by IHC. We assessed the efficacy of capsaicin‐mediated afferent denervation in preventing the physiological responses to activation of the renal afferent nerves. Methods: Conscious Sprague‐Dawley rats implanted with an ICV cannula, having undergone sham (S) or renal afferent nerve denervation (ADNX) (capsaicin 33mM), received IV and IR infusions of bradykinin (BK) (5‐40 μg/kg/min) and adenosine (A) (2‐12 μg/min). All animals then received ICV guanabenz (50ug) (N=4/gp). HR, MAP and sodium excretion were continuously monitored. Results : IR BK dose‐dependently increased MAP and HR in sham animals and had no effect on MAP or HR in ADNX rats (BK 40 μg/kg/min; peak ΔHR [bpm] S +61±8 vs ADNX ‐5±3, P<0.05; peak ΔMAP [mmHg] S +19±3 vs ADNX +0.6±2, P<0.0.5). IV BK did not alter MAP or HR at any dose tested in S or ADNX rats. IR, but not IV, adenosine evoked a dose‐dependent increase in natriuresis in sham animals, a response that was abolished following ADNX (A 12 μg/min; peak ΔUNaV [ueq/min] S +18.7±3 vs ADNX +2±0.4, P<0.05). In both sham and ADNX rats, ICV guanabenz evoked profound bradycardia, hypotension and natriuresis (guanabenz 50 μg; peak ΔUNaV [μeq/min] S +13.4±1 vs ADNX +12.8±1). Conclusion: These data provide compelling evidence that the recently described technique of capsaicin mediated afferent renal denervation prevents the physiological responses to intrarenal administration of established activators of the renal afferent nerves. Further, central α 2 ‐adrenoceptor activation evoked a profound natriuretic response mediated by suppression of efferent nerve activity in sham and ADNX rats. This indicates the presence of viable and functional renal efferent nerves following ADNX. Collectively these data demonstrate it possible to selectively denervate renal afferent nerves without affecting the function of the renal efferent nerves. Grant Funding Source : Support by R01HL107330 & K02HL112718A1