Sympathoexcitation by Inhibition of SK Channel Activity in the Hypothalamic PVN is Attenuated by Local AT1 Receptor Blockade

Small conductance Ca2+ activated K+ (SK) channels act as negative feedback regulators of neuronal excitability. We have reported that SK channels expressed in the paraventricular nucleus (PVN) are involved in controlling neuronal activity, sympathetic nerve activity (SNA) and arterial pressure (AP). Blockade of SK channels in the pre-sympathetic PVN neurons increases neuronal excitability, SNA and AP. Here we investigated the effect of angiotensin II type 1 receptor (AT1R) blockade on the sympathoexcitatory and presser responses elicited by the inhibition of SK channels in the PVN. In anesthetized rats, PVN microinjection of SK channel blocker with apamin (12.5 pmol, 50nl) (n=7) increased splanchnic SNA (SSNA) (278 ± 50%), renal SNA (RSNA) (193 ± 12%), and mean AP (MAP) (32 ± 4mmHg). Pre-treatment with PVN injection of losartan (20 nmol), an AT1R antagonist, significantly attenuated (n=6) the elevated SSNA (129 ± 37%; p<.05 vs vehicle control), RSNA (84 ± 40%; p<.05 vs vehicle control), and MAP (10 ± 6mmH...