Role of the afferent renal nerves in sodium homeostasis and blood pressure regulation in rats

Abstract

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.

Sensory Afferent Renal Nerve Activated Gαi2 Subunit Proteins Mediate the Natriuretic, Sympathoinhibitory and Normotensive Responses to Peripheral Sodium Challenges

“…Collectively our current data, which replicate our prior study in Sprague Dawley rats and the Dahl Salt resistant rat in which ADNX immediately prior to high salt intake evoked the salt sensitivity of blood pressure (Frame et al, 2019), suggest that the sympathoinhibitory afferent renal nerve reno-renal reflex is a protective mechanism against the initial increase in blood pressure observed following high salt intake -an observation supported by prior studies following generalized sensory afferent denervation via dorsal rhizotomy or subcutaneous capsaicin treatment in SD rats (Wang et al, 1998(Wang et al, , 2001Kopp et al, 2003). Given that the renal afferent nerves have projections to the PVN our studies suggest that brain Gαi 2 protein-gated normotensive sympathoinhibitory pathways are upregulated by chronic elevated dietary sodium intake at the level of the kidney via the sensory renal afferent nerves.…”

“…Kidneys were harvested from rats following completion of the experimental protocol, and the renal pelvis was extracted, flash frozen and stored at −80 • C. Renal pelvic GCRP content was determined with an ELISA (no. 589001, Cayman Chemical Co., Ann Arbor, MI, United States) as per manufacturers' instructions (Foss et al, 2015;Frame et al, 2019).…”

Inhibition of microglial activation in rats attenuates paraventricular nucleus inflammation in Gαi2 protein‐dependent, salt‐sensitive hypertension

“…Radiotelemetry data were collected, stored and analysed using Dataquest A.R.T. v.4.2 software (Data Sciences International, St. Paul, MN, USA) (Brouwers, Smolders, Wainford, & Dupont, ; Frame, Carmichael, Kuwabara, Cunningham, & Wainford, ; Wainford et al., ).…”

“…Male Sprague-Dawley rats weighing 275-300 g were purchased from (Brouwers, Smolders, Wainford, & Dupont, 2015;Frame, Carmichael, Kuwabara, Cunningham, & Wainford, 2019;Wainford et al, 2015).…”

Sensory signals mediating high blood pressure via sympathetic activation: role of adipose afferent reflex

“…Afferent fibers with sensory receptor endings have been described in heart (117,120,138,177), aorta (27,116,137), carotid body (37, 79,85), pulmonary veins (118,175), blood vessels (109,159), adrenal glands (56,152,173), visceral organs (14, 70,93,139), kidney (54,95,122,187), skeletal muscle (87,110), and adipose tissue (7,9,162,185). In physiological conditions, afferent nerve activity is critical for maintaining vascular tone, coronary vascular blood flow, water and electrolyte balance, renal microcirculation, lipolysis, and lipid redistribution.…”