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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Osmoregulatory fluid intake but not hypovolemic thirst is intact in mice lacking angiotensin

¹Howard Florey Institute and ²Department of Physiology, University of Melbourne, Parkville, Victoria; ³St Vincent's Institute of Medical Research and the Department of Medicine, University of Melbourne, St Vincent's Hospital, Fitzroy, Victoria; and ⁴Department of Physiology, Monash University, Clayton, Victoria; Australia

Submitted 26 November 2007 ; accepted in final form 18 February 2008

Water intakes in response to hypertonic, hypovolemic, and dehydrational stimuli were investigated in mice lacking angiotensin II as a result of deletion of the angiotensinogen gene (Agt–/– mice), and in C57BL6 wild-type (WT) mice. Baseline daily water intake in Agt–/– mice was approximately threefold that of WT mice because of a renal developmental disorder of the urinary concentrating mechanisms in Agt–/– mice. Intraperitoneal injection of hypertonic saline (0.4 and 0.8 mol/l NaCl) caused a similar dose-dependent increase in water intake in both Agt–/– and WT mice during the hour following injection. As well, Agt–/– mice drank appropriate volumes of water following water deprivation for 7 h. However, Agt–/– mice did not increase water or 0.3 mol/l NaCl intake in the 8 h following administration of a hypovolemic stimulus (30% polyethylene glycol sc), whereas WT mice increased intakes of both solutions during this time. Osmoregulatory regions of the brain [hypothalamic paraventricular and supraoptic nuclei, median preoptic nucleus, organum vasculosum of the lamina terminalis (OVLT), and subfornical organ] showed an increased number of neurons exhibiting Fos-immunoreactivity in response to intraperitoneal hypertonic NaCl in both Agt–/– mice and WT mice. Polyethylene glycol treatment increased Fos-immunoreactivity in the subfornical organ, OVLT, and supraoptic nuclei in WT mice but only increased Fos-immunoreactivity in the supraoptic nucleus in Agt–/– mice. These data show that brain angiotensin is not essential for the adequate functioning of neural pathways mediating osmoregulatory thirst. However, angiotensin II of either peripheral or central origin is probably necessary for thirst and salt appetite that results from hypovolemia.

angiotensinogen gene; hypertonicity; dehydration; hypovolemia; fos

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