Veitenheimer BJ, Engeland WC, Guzman PA, Fink GD, Osborn JW. Effect of global and regional sympathetic blockade on arterial pressure during water deprivation in conscious rats. Am J Physiol Heart Circ Physiol 303: H1022-H1034, 2012. First published August 17, 2012; doi:10.1152/ajpheart.00413.2012.-Forty-eight hours of water deprivation (WD) in conscious rats results in a paradoxical increase in mean arterial pressure (MAP). Previous studies suggest this may be due to increased sympathetic nerve activity (SNA). However, this remains to be investigated in conscious, freely behaving animals. The purpose of this study was to determine, in conscious rats, the role of the sympathetic nervous system (SNS) in mediating WD-induced increases in MAP and to identify which vascular beds are targeted by increased SNA. Each rat was chronically instrumented with a radiotelemetry transmitter to measure MAP and heart rate (HR) and an indwelling venous catheter for plasma sampling and/or drug delivery. MAP and HR were continuously measured during a 2-day baseline period followed by 48 h of WD and then a recovery period. By the end of the WD period, MAP increased by ϳ15 mmHg in control groups, whereas HR did not change significantly. Chronic blockade of ␣ 1/1-adrenergic receptors significantly attenuated the WD-induced increase in MAP, suggesting a role for global activation of the SNS. However, the MAP response to WD was unaffected by selective denervations of the hindlimb, renal, or splanchnic vascular beds, or by adrenal demedullation. In contrast, complete adrenalectomy (with corticosterone and aldosterone replaced) significantly attenuated the MAP response to WD in the same time frame as ␣ 1/1-adrenergic receptor blockade. These results suggest that, in conscious water-deprived rats, the SNS contributes to the MAP response and may be linked to release of adrenocortical hormones. Finally, this sympathetically mediated response is not dependent on increased SNA to one specific vascular bed. osmolality; sympathetic nerve activity; water deprivation; denervation; adrenal cortex WATER DEPRIVATION (WD) over long periods of time increases plasma osmolality and decreases blood volume. Despite the hypovolemia induced by WD, it has been reported that mean arterial pressure (MAP) is not only maintained but actually increases in conscious rats (4,8,46). The mechanisms mediating this paradoxical increase in MAP are not clear, but previous studies have shown that WD is accompanied by elevations in the renin-angiotensin-aldosterone system (4, 14, 16), plasma vasopressin and corticosterone (14,17,32), and sympathetic nerve activity (SNA) (10,53,55,56). In this study, we investigated the sympathetic component of the MAP response to WD.Although it is generally accepted that the sympathetic nervous system is activated during WD to support MAP, the evidence supporting this is not entirely conclusive. Studies in which plasma norepinephrine was measured as an indicator of global sympathetic activity have been inconsistent, with some showing no ch...