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The role of Gαi 2 proteins in the regulation of PVN neuronal activation in response to isotonic volume expansion in conscious rats
Author(s) -
Carmichael Casey Y,
Patel Neha M,
Wipfler Rachel E,
Wainford Richard D
Publication year - 2016
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.30.1_supplement.964.13
Subject(s) - endocrinology , chemistry , medicine , tonicity , diuretic , diuresis , saline , isotonic saline , hypertonic saline , isotonic , excretion , renal function
Aim An acute volume expansion (VE) evokes inhibition of sympathetic outflow and the paraventricular nucleus (PVN) is a key region involved in this response. Extending our prior studies demonstrating a role of CNS Gαi 2 proteins in PVN neuronal activation during acute hypertonic saline challenge, we determined the role of brain Gαi 2 proteins in PVN neuronal activation during an acute VE. Methods 24‐h intracerebroventricular scrambled (SCR) or Gαi 2 oligodeoxynucleotide (ODN; 25μg/5μl)‐pretreated conscious Sprague‐Dawley rats were IV infused with isotonic saline (0.9% w/v NaCl) equal to 10% of body weight in 10‐min, followed by a maintenance infusion of 0.5 ml/min for 90‐min, and then a physiological infusion of 20 μl/min for 20‐min. Rats were monitored for changes in cardiovascular and urine excretory parameters and sacrificed at control (C) or 120‐min post‐VE for PVN cFos IHC. Results In both SCR and Gαi 2 ODN pretreated rats, acute isotonic VE produced no significant change in systemic cardiovascular parameters ( P >0.05). VE evoked a significant increase in urine flow rate (V) and urinary sodium excretion (UNaV) in SCR ODN pretreated rats, while the magnitude of the diuretic and natriuretic response was attenuated in Gαi 2 ODN pretreated rats (peak Δ UNaV [μeq/min] SCR: 101.29±4.20 vs. Gαi 2 : 63.12±9.78, P <0.05). No difference in the number of PVN Fos + cells was observed between ODN pretreated groups at control. Significant increases in the number of Fos + PVN magnocellular and parvocellular neurons were observed post‐VE in both SCR and Gαi 2 ODN groups as compared to C ( P <0.05). Gαi 2 ODN rats exhibited significantly less activated magnocellular (120‐min [Fos + cells] SCR: 24±3 vs Gαi 2 : 16±2, P <0.05) and parvocellular neurons (120‐min [Fos + cells] SCR: 168±6 vs Gαi 2 : 102±4, P <0.05) as compared to their SCR ODN counterparts following VE ( P <0.05). Conclusion Endogenous brain Gαi 2 proteins contribute to the activation of PVN neurons during isotonic VE to maintain body fluid homeostasis. Owing to the established sympathoinhibitory actions of PVN parvocellular neurons post VE, we speculate Gαi 2 proteins are central to the activation of sympathoinhibitory parvocelluar neurons. This hypothesis is supported by our prior data demonstrating 1) CNS Gαi 2 proteins are essential to facilitate the suppression of renal sympathetic nerve traffic during acute VE and 2) CNS Gαi 2 proteins mediate activation of PVN parvocellular neurons and sympathoinhibition in response to an acute bolus sodium challenge. Collectively, these data highlight a novel role of PVN Gαi 2 proteins in the acute neural sympathoinhibitory pathways that regulate fluid and electrolyte homeostasis. Further, impairments in these neural pathways potentially contribute to altered sympathetic outflow and sodium retention in the pathophysiology of hypertension. Support or Funding Information NIH HL107330 K02HL112718