Activity of Hypothalamic Paraventricular Nucleus (PVN) Neurons Controls Sympathetic Nerve Activity (SNA) and Respiration in Angiotensin II (AngII)‐Salt Hypertensive Rats: No Role for Local NMDA Receptors (NMDAR)

Abstract

Rats consuming high salt (2% NaCl) and treated with AngII (150 ng/kg/min, s.c.) develop hypertension that is dependent on ongoing SNA. In telemetric recordings, we have determined that AngII‐Salt hypertensive (HT) rats also have increased respiration rate. Because PVN neurons innervate sympathetic and respiratory network components, we hypothesized that PVN neuronal activity supports SNA and respiration more in AngII‐Salt HT (n=6) than control (0.4 % NaCl diet, n=9) rats. With ETCO2 set at 5%, mean arterial pressure (MAP) was ~13 mmHg higher in AngII‐Salt HT rats than controls, but burst frequencies of phrenic nerve activity (PNA) were similar. In control rats (n=4), inhibition of PVN (muscimol, 100 pmol in 50 nl/side) had little effect on splanchnic SNA (−7 ± 4 %) or MAP (−1 ± 2 mmHg), but both were reduced (P<0.05) in AngII‐Salt HT rats (splanchnic SNA: −22 ± 3 %, MAP: −39 ± 6 mmHg, n=3). PVN muscimol also reduced PNA bursts (amplitude: −7 ± 4 %, AUC: −15 ± 1 %) and neural minute ventilation (−7 ± 4 %), but only in AngII‐Salt HT rats. Support of PVN neuronal activity by local NMDAR was tested by injection of the antagonist AP5 (200 pmol in 50 nl). In control (n=5) and AngII‐Salt HT (n=4) rats, AP5 had no affect on SNA, PNA or MAP. These data indicate that PVN neuronal activity plays an enhanced role in supporting SNA, inspiratory activity, and MAP in AngII‐Salt HT rats, but this does not depend on local NMDAR. Support: HL102310 & HL088052 (GMT)