AT(1)-receptor blockade in the hypothalamic PVN reduces central hyperosmolality-induced renal sympathoexcitation

Autonomic neurons in the hypothalamic paraventricular nucleus (PVN) are inn ervated by osmotic-sensitive regions of the lamina terminalis, receive inpu t from ANG II-containing cells, and express AT(1) ANG II receptors. Therefo re, we hypothesized that ANG II actions within the PVN could underlie hyper osmolality-induced increases in renal sympathetic nerve activity (RSNA). In anesthetized baroreceptor-denervated rats, graded concentrations of NaCl ( 0.30, 0.9, 1.5, and 2.1 osmol/l) were injected (300 mul) centrally via the internal carotid artery (ICA) and produced corresponding increases in mean arterial pressure (MAP) and RSNA. In addition, equivalent hyperosmotic load s (1.5 osmol/l) of NaCl, glucose, and mannitol each significantly (P < 0.05 ) increased MAP and RSNA. The same stimuli had no effect when administered intravenously. Bilateral PVN microinjections (100 nl) of the AT(1)-receptor antagonist losartan (80 nmol) before osmotic challenge had no effect on re sting RSNA but significantly (P, 0.05) reduced RSNA responses to hyperosmot ic NaCl (n = 7), glucose (n = 6), and mannitol (n = 6). Increases in RSNA e voked by hyperosmotic NaCl were significantly (P < 0.05) attenuated similar to 20 min after losartan injection and recovered within 60-120 min. In con trast, losartan outside the PVN as well as vehicle (saline) within the PVN failed to alter RSNA responses to ICA hyperosmotic NaCl. Results suggest th at elevated RSNA after central sodium/osmotic activation is mediated, at le ast in part, by a synaptic mechanism involving AT(1)-receptor activation wi thin the PVN.