TY - JOUR
T1 - Role of the afferent renal nerves in sodium homeostasis and blood pressure regulation in rats
AU - Frame, Alissa A.
AU - Carmichael, Casey Y.
AU - Kuwabara, Jill T.
AU - Cunningham, J. Thomas
AU - Wainford, Richard D.
N1 - Funding Information:
informationThis work was supported by NIH R56 AG057687, R01 HL139867, R01 HL141406, R01 HL107330 and K02 HL112718 and AHA 16MM32090001 and 17GRNT33670023 to R.D.W. and NIH F31 DK116501 to A.A.F. The work of J.T.C. was supported by NIH R01 HL141406 to R.D.W.A.A.F, C.Y.C., J.T.C. and R.D.W. conceived and designed research; A.A.F, C.Y.C., J.T.K., J.T.C. and R.D.W performed experiments; A.A.F, C.Y.C., J.T.C. and R.D.W JDM, PC, and RDW analysed data; A.A.F, C.Y.C., J.T.C. and R.D.W interpreted results of experiments; A.A.F. and R.D.W prepared figures; A.A.F, J.T.C. and R.D.W drafted manuscript; A.A.F, J.T.C. and R.D.W edited and revised manuscript. All authors have read and approved the final version of this manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed.
Publisher Copyright:
© 2019 The Authors. Experimental Physiology Published by John Wiley & Sons Ltd on behalf of The Physiological Society
PY - 2019/8/1
Y1 - 2019/8/1
N2 - New Findings: What is the central question of this study? What are the differential roles of the mechanosensitive and chemosensitive afferent renal nerves in the reno-renal reflex that promotes natriuresis, sympathoinhibition and normotension during acute and chronic challenges to sodium homeostasis? What is the main finding and its importance? The mechanosensitive afferent renal nerves contribute to an acute natriuretic sympathoinhibitory reno-renal reflex that may be integrated within the paraventricular nucleus of the hypothalamus. Critically, the afferent renal nerves are required for the maintenance of salt resistance in Sprague–Dawley and Dahl salt-resistant rats and attenuate the development of Dahl salt-sensitive hypertension. Abstract: These studies tested the hypothesis that in normotensive salt-resistant rat phenotypes the mechanosensitive afferent renal nerve (ARN) reno-renal reflex promotes natriuresis, sympathoinhibition and normotension during acute and chronic challenges to fluid and electrolyte homeostasis. Selective ARN ablation was conducted prior to (1) an acute isotonic volume expansion (VE) or 1 m NaCl infusion in Sprague–Dawley (SD) rats and (2) chronic high salt intake in SD, Dahl salt-resistant (DSR), and Dahl salt-sensitive (DSS) rats. ARN responsiveness following high salt intake was assessed ex vivo in response to noradrenaline and sodium concentration (SD, DSR and DSS) and via in vivo manipulation of renal pelvic pressure and sodium concentration (SD and DSS). ARN ablation attenuated the natriuretic and sympathoinhibitory responses to an acute VE [peak natriuresis (µeq min−1) sham 52 ± 5 vs. ARN ablation 28 ± 3, P < 0.05], but not a hypertonic saline infusion in SD rats. High salt (HS) intake enhanced ARN reno-renal reflex-mediated natriuresis in response to direct increases in renal pelvic pressure (mechanoreceptor stimulus) in vivo and ARN responsiveness to noradrenaline ex vivo in SD, but not DSS, rats. In vivo and ex vivo ARN responsiveness to increased renal pelvic sodium concentration (chemoreceptor stimulus) was unaltered during HS intake. ARN ablation evoked sympathetically mediated salt-sensitive hypertension in SD rats [MAP (mmHg): sham normal salt 102 ± 2 vs. sham HS 104 ± 2 vs. ARN ablation normal salt 103 ± 2 vs. ARN ablation HS 121 ± 2, P < 0.05] and DSR rats and exacerbated DSS hypertension. The mechanosensitive ARNs mediate an acute sympathoinhibitory natriuretic reflex and counter the development of salt-sensitive hypertension.
AB - New Findings: What is the central question of this study? What are the differential roles of the mechanosensitive and chemosensitive afferent renal nerves in the reno-renal reflex that promotes natriuresis, sympathoinhibition and normotension during acute and chronic challenges to sodium homeostasis? What is the main finding and its importance? The mechanosensitive afferent renal nerves contribute to an acute natriuretic sympathoinhibitory reno-renal reflex that may be integrated within the paraventricular nucleus of the hypothalamus. Critically, the afferent renal nerves are required for the maintenance of salt resistance in Sprague–Dawley and Dahl salt-resistant rats and attenuate the development of Dahl salt-sensitive hypertension. Abstract: These studies tested the hypothesis that in normotensive salt-resistant rat phenotypes the mechanosensitive afferent renal nerve (ARN) reno-renal reflex promotes natriuresis, sympathoinhibition and normotension during acute and chronic challenges to fluid and electrolyte homeostasis. Selective ARN ablation was conducted prior to (1) an acute isotonic volume expansion (VE) or 1 m NaCl infusion in Sprague–Dawley (SD) rats and (2) chronic high salt intake in SD, Dahl salt-resistant (DSR), and Dahl salt-sensitive (DSS) rats. ARN responsiveness following high salt intake was assessed ex vivo in response to noradrenaline and sodium concentration (SD, DSR and DSS) and via in vivo manipulation of renal pelvic pressure and sodium concentration (SD and DSS). ARN ablation attenuated the natriuretic and sympathoinhibitory responses to an acute VE [peak natriuresis (µeq min−1) sham 52 ± 5 vs. ARN ablation 28 ± 3, P < 0.05], but not a hypertonic saline infusion in SD rats. High salt (HS) intake enhanced ARN reno-renal reflex-mediated natriuresis in response to direct increases in renal pelvic pressure (mechanoreceptor stimulus) in vivo and ARN responsiveness to noradrenaline ex vivo in SD, but not DSS, rats. In vivo and ex vivo ARN responsiveness to increased renal pelvic sodium concentration (chemoreceptor stimulus) was unaltered during HS intake. ARN ablation evoked sympathetically mediated salt-sensitive hypertension in SD rats [MAP (mmHg): sham normal salt 102 ± 2 vs. sham HS 104 ± 2 vs. ARN ablation normal salt 103 ± 2 vs. ARN ablation HS 121 ± 2, P < 0.05] and DSR rats and exacerbated DSS hypertension. The mechanosensitive ARNs mediate an acute sympathoinhibitory natriuretic reflex and counter the development of salt-sensitive hypertension.
KW - afferent renal nerves
KW - blood pressure
KW - sodium homeostasis
UR - http://www.scopus.com/inward/record.url?scp=85070851419&partnerID=8YFLogxK
U2 - 10.1113/EP087700
DO - 10.1113/EP087700
M3 - Article
C2 - 31074108
AN - SCOPUS:85070851419
SN - 0958-0670
VL - 104
SP - 1306
EP - 1323
JO - Experimental Physiology
JF - Experimental Physiology
IS - 8
ER -