Acute inhibition of the hypothalamic paraventricular nucleus decreases renal sympathetic nerve activity and arterial blood pressure in water-deprived rats

Abstract

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 ...

AT1 and glutamatergic receptors in paraventricular nucleus support blood pressure during water deprivation

“…As previously reported (42,43), we observed that acute inhibition of PVN after microinjection of muscimol rapidly decreased arterial BP in water-deprived rats. The rapid nature of the depressor response, as well as previous simultaneous measurements of renal and lumbar sympathetic activity (42,43), indicates that the fall in pressure is largely mediated by decreases in sympathetic activity.…”

“…1). In contrast, as previously reported (42,43), muscimol administration in water-deprived rats promptly decreased BP, and the depressor response ex-ceeded both the response to aCSF in water-deprived rats and the response to muscimol exhibited by water-replete rats. Muscimol also decreased heart rate in water-deprived rats (Ϫ30 Ϯ 7 beats/min) relative to control aCSF injections (0 Ϯ 5 beats/min) (P Ͻ 0.05).…”

“…Recent studies indicate that sympathoexcitatory neurons in the paraventricular nucleus (PVN) contribute to this activation, since acute blockade of the PVN results in profound decreases in arterial blood pressure (BP) and sympathetic activity (42,43). Moreover, PVN neurons that project to the spinal cord, which houses sympathetic preganglionic neurons, or to the rostral ventrolateral medulla (RVLM), a hindbrain region responsible for the basal activity of many sympathetic nerves, express c-fos after water deprivation (41,42), indirectly suggesting activation.…”

In Vivo Discharge Properties of Hypothalamic Paraventricular Nucleus Neurons With Axonal Projections to the Rostral Ventrolateral Medulla

“…Moreover, reductions of SNA in response to PVN inhibition or blockade of excitatory inputs are more pronounced in water deprived (Freeman and Brooks 2007;Stocker et al 2004b and hypertensive (Allen 2002;Li and Pan 2007) rats. These findings indicate that PVN neuronal activity contributes to both the maintenance of resting SNA and to the elevation of SNA under physiologic and disease conditions.…”

“…In anesthetized rats, for example, studies have shown that acute inhibition of PVN neuronal activity or blockade of excitatory inputs reduces ongoing renal SNA (RSNA) (Akine et al 2003;Allen 2002;Stocker et al 2004b, lumbar SNA , and ABP (Akine et al 2003;Allen 2002;Freeman and Brooks 2007;Stocker et al 2004b. It is noteworthy that reductions of SNA in response to PVN inhibition are more pronounced in water-deprived (Freeman and Brooks 2007;Stocker et al 2004b and hypertensive (Akine et al 2003;Allen 2002;Li and Pan 2007) rats, suggesting an increased contribution of PVN neuronal activity to the maintenance of resting SNA.…”