Submitted on November 26, 2007
Accepted on February 18, 2008
Osmoregulatory fluid intake but not hypovolemic thirst is intact in mice lacking angiotensin
Michael J. McKinley1*, Lesley L. Walker2, Theodora Alexiou2, Andrew M Allen3, Duncan J. Campbell4, Robert Di Nicolantonio3, Brian J. Oldfield5, and Derek A. Denton3
1 Howard Florey Institute, Florey Neuroscience Institutes, Parkville, Victoria, Australia
2 Howard Florey Institute, Florey Neuroscience Institutes, Melbourne, Victoria, Australia
3 Physiology, University of Melbourne, Melbourne, Victoria, Australia
4 St Vincent's Institute, University of Melbourne, Fitzroy, Victoria, Australia
5 Physiology, Monash University, Melbourne, Victoria, Australia; , Australia
* To whom correspondence should be addressed. E-mail: michael.mckinley{at}florey.edu.au.
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 mice (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 (i.p.) 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 hours. However, Agt-/- mice did not increase water or 0.3 mol/l NaCl intake in the 8 hours following administration of a hypovolemic stimulus (subcutaneous 30% polyethylene glycol), 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 increased number of neurons exhibiting Fos-immunoreactivity in response to i.p. hypertonic NaCl in both Agt-/- mice and WT-mice. PEG 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.
