Burst patterning of hypothalamic paraventricular nucleus-driven sympathetic nerve activity in ANG II-salt hypertension

Abstract

ANG II-salt hypertension selectively increases splanchnic sympathetic nerve activity (sSNA), but the extent to which this reflects increased respiratory versus cardiac rhythmic bursting is unknown. Here, integrated sSNA was elevated in ANG II-infused rats fed a high-salt (2% NaCl) diet (ANG II-HSD) compared with vehicle-infused rats fed a normal-salt (0.4% NaCl) diet (Veh-NSD; P < 0.01). Increased sSNA was not accompanied by increased inspiratory or expiratory bursting, consistent with no group difference in central inspiratory drive. Consistent with preserved inhibitory baroreflex entrainment of elevated sSNA in ANG II-HSD rats, the time integral (P < 0.05) and amplitude (P < 0.01) of cardiac rhythmic sSNA were increased. Consistent with activity of hypothalamic paraventricular nucleus (PVN) neurons supporting basal SNA in ANG II-salt hypertension, inhibition of PVN with the GABA-A receptor agonist muscimol reduced mean arterial pressure (MAP) and integrated sSNA only in the ANG II-HSD group (P < 0.001). PVN inhibition had no effect on respiratory rhythmic sSNA bursting in either group but reduced cardiac rhythmic sSNA in ANG II-HSD rats only (P < 0.01). The latter likely reflected reduced inhibitory baroreflex entrainment subsequent to the fall of MAP. Of note is that MAP as well as integrated and rhythmic burst patterns of sSNA were similar in vehicle-infused rats whether they were fed a normal or high-salt diet. Findings indicate that PVN neurons support elevated sSNA in ANG II-HSD rats by driving a tonic component of activity without altering respiratory or cardiac rhythmic bursting. Because sSNA was unchanged in Veh-HSD rats, activation of PVNdriven tonic sSNA appears to require central actions of ANG II. NEW & NOTEWORTHY ANG II-salt hypertension is strongly neurogenic and depends on hypothalamic paraventricular nucleus (PVN)-driven splanchnic sympathetic nerve activity (sSNA). Here, respiratory and cardiac bursts of sSNA were preserved in ANG II-salt rats and unaltered by PVN inhibition, suggesting that PVN neurons drive a tonic component of sSNA rather than modulating dominant patterns of burst discharge.