Acute inhibition of the hypothalamic paraventricular nucleus decreases renal sympathetic nerve activity and arterial blood pressure in water-deprived rats. Am J Physiol Regul Integr Comp Physiol 286: R719-R725, 2004. First published December 11, 2003 10.1152/ ajpregu.00494.2003.-The present study was performed to determine whether sympathetic outflow and arterial blood pressure in waterdeprived rats are dependent on the ongoing neuronal activity of the hypothalamic paraventricular nucleus (PVN). Renal sympathetic nerve activity (RSNA), mean arterial blood pressure (MAP), and heart rate were recorded in urethane-␣-chloralose-anesthetized rats that were deprived of water but not food for 48 h before experiments. Acute inhibition of the PVN by bilateral microinjection of the GABA A agonist muscimol (100 pmol/side) significantly decreased RSNA in water-deprived rats (Ϫ26.7 Ϯ 4.7%, n ϭ 7) but was without effect in control rats (1.3 Ϯ 6.3%, n ϭ 7). Similarly, injection of muscimol produced a greater decrease in MAP in water-deprived rats than in control rats (Ϫ46 Ϯ 3 vs. Ϫ16 Ϯ 3 mmHg, respectively), although baseline MAP was not different between groups (105 Ϯ 4 vs. 107 Ϯ 4 mmHg, respectively). Neither bilateral microinjection of isotonic saline vehicle (100 nl/side) into the PVN nor muscimol (100 pmol/side) outside the PVN altered RSNA or MAP in either group. In addition, ganglionic blockade with hexamethonium (30 mg/kg iv) significantly decreased MAP in both groups; however, the decrease in MAP was significantly greater in water-deprived rats than in control rats (62 Ϯ 2 vs. 48 Ϯ 2 mmHg, respectively). Collectively, these findings suggest that sympathetic outflow contributes more to the maintenance of blood pressure in the water-deprived rat, and this depends, at least partly, on the ongoing activity of PVN neurons. dehydration; hypovolemia; hyperosmolality; angiotensin II; GABAA receptor WATER DEPRIVATION DEPLETES the intracellular and extracellular compartments of water and consequently increases plasma osmolality (P osmol ) and decreases intravascular volume. Despite the contraction of blood volume, arterial blood pressure (ABP) is maintained within a normal range by both hormonal and neural factors. Indeed, studies have reported increased activity of the peripheral renin-angiotensin system (31, 43, 49), increased circulating levels of vasopressin (5, 46, 49), and increased sympathoadrenal activity (14,40,41,49) in waterdeprived rats. The latter is reflected by the increased levels of circulating catecholamines (49), tachycardia (14,40,41), and elevated sympathetic nerve activity when expressed as a percentage of the baroreflex maximum (40). Collectively, these observations suggest that sympathetic outflow is elevated in water-deprived rats; however, the neural circuits that underlie this response are not known.Neuroanatomical and functional studies suggest the hypothalamic paraventricular nucleus (PVN) plays an important role in the regulation of ABP and sympathetic outflow. The PVN receives input from neuronal ...