Chronic chemogenetic activation of OVLT neurons alters body fluid homeostasis and sympathetically‐mediated hypertension

The organum vascuolsum of the lamina terminalis (OVLT) contains a specialized group of neurons that can sense changes in extracellular NaCl concentrations to alter body fluid homeostasis and arterial blood pressure (ABP). Acute excitation of these neurons with hypertonic NaCl produces a sympathetically‐mediated increase in ABP. The purpose of the present study was to determine whether chronic activation of OVLT neurons produces hypertension. Rats were instrumented with telemetry devices and received an OVLT‐targeted injection of rAAV2‐hSyn‐HM4D(Gi)‐mCherry (3×10 12 particles/mL, 50nL). Animals were returned to home cages to recover for 4 weeks with access to 0.1% NaCl chow and 0.9% NaCl drinking solution. After a 3‐day recording of baseline ABP and heart rate, clozapine‐N‐oxide was added to the 0.9% drinking solution for 7 days to produce a daily dose of ~3 mg/kg body weight. The concentration of the clozapine‐N‐oxide was adjusted daily to account for changes in fluid intake. Administration of clozapine‐N‐oxide to OVLT‐HM4D(Gi)‐expressing rats significantly increased 24‐h fluid intake from baseline to Day 7 (60±10 vs 178±29mL; n=4, P<0.01). Chronic activation of OVLT neurons significantly increased 24‐h mean ABP from baseline values versus Day 7 (97±2 vs 106±1 mmHg; n=4, P<0.05). Heart rate decreased from baseline values versus Day 7 (385±14 vs 330±26 bpm; n=4, P<0.05). Ganglionic blockade with hexamethonium (30 mg/kg, ip) produced a greater fall in mean ABP at Day 7 versus baseline values (baseline: −38±6 mmHg vs −53±5 mmHg; n=4, P<0.05). In addition, chronic activation of OVLT neurons increased 24‐h systolic blood pressure variability, calculated by the SD of systolic blood pressure, from baseline values versus Day 7 (9.1±0.4 vs 11.2±0.3 mmHg, P<0.05). Collectively, these observations suggest the chronic activation of OVLT neurons produces profound changes in body fluid homeostasis and cardiovascular regulation as reflected by 3x‐increase in fluid intake, a sympathetically‐mediated hypertension, and an increase in systolic blood pressure variability. Support or Funding Information NIH R01 113270 and 128388 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .