Impaired PVN neuronal activity in response to acute sodium challenge drives persistent elevations in MAP in conscious rats lacking CNS Gαi2 proteins (686.6)

Abstract

Aim: We have reported CNS Gαi2 proteins mediate the sympathoinhibitory responses to chronic high salt‐intake. These studies assessed the role of CNS Gαi2 proteins in the activity of PVN neurons in response to acute sodium challenge.Methods: 24‐h ICV Gαi2 or SCR oligodeoxynucleotide (ODN; 25μg/5μl)‐pretreated conscious Sprague‐Dawley rats were monitored for changes in MAP in response to IV bolus NaCl (3M; 0.14 ml/100g). Separate groups of rats were sacrificed at time of the peak MAP change (40 min post‐IV NaCl) and Fos IHC was performed (N=6/gp).Results: No difference was observed in sodium‐evoked peak change in MAP between treatment groups (IV 3M NaCl ΔMAP [mmHg] SCR: 13±4 vs. Gαi2: 10±3), however MAP returned to control levels by 100 min in SCR but not Gαi2 treated rats (MAP 100min post‐IV NaCl [mmHg] SCR: 134±2 vs. Gαi2: 146±3, P<0.05). In SCR, but not Gαi2, treated rats, an IV NaCl bolus produced significant reduction in Fos immunoreactivity ([PVN Fos positive cells] SCR control: 95±9 vs. post NaCl: 5±1, p<0.05, Gαi2 control 90±13: vs. post NaCl: 66±9).Conclusion: These data reveal a novel role of CNS Gαi2 proteins in the regulation of the neuronal response within the hypothalamic PVN to an acute sodium challenge that significantly elevates MAP. The sodium‐induced decrease in Fos‐positive PVN cells in SCR ODN rats likely reflects inhibition of neuronal activity facilitating the return of MAP to basal levels. In Gαi2 pretreated rats, failure to inhibit PVN neuronal activity represents a neural mechanism by which impairment of Gαi2 signal‐transduction pathways may contribute to the pathophysiology of salt‐sensitive hypertension.Grant Funding Source: Supported by RO1 HL107330, K02 HL112718, & T32 GM008541