Poster Presentation Neuropathophysiology - an ISH satellite 2012

Characterisation of mice with selective AT1A receptor deletion from catecholaminergic neurons. (#55)

Nikola Jancovski 1 , Angela A Connelly 1 , Jaspreet K Bassi 1 , David Carter 1 , Elyse Stevens 1 , John Brandi 1 , Geoffrey A Head 2 , Andrew M Allen 1
  1. Department of Physiology, The University of Melbourne, Parkville, VIC, Australia
  2. Neuropharmacology Laboratory, Baker IDI Heart and Diabetes Research Institute , Melbourne, VIC, Australia

Background: Angiotensin II (Ang II) has well established roles in the regulation of blood pressure (BP) and fluid and electrolyte regulation. However manipulation of brain Ang II can also induce metabolic changes including lean phenotype, increased metabolic rate, or increased oxygen consumption. It is believed that some of these actions are mediated via activation of the Ang II type 1A receptor (AT1AR). The present study aimed to investigate whether targeted deletion of AT1ARs from the catecholaminergic cells affects the baseline metabolic parameters and blood pressure (BP). Methods: Mice with cell-selective deletion of the AT1AR from catecholaminergic cells were generated by crossing AT1AR floxed (AT1ARfl/fl) mice with mice expressing cre-recombinase (Cre) under the control of the tyrosine hydroxylase (TH) promoter. Two different genotypes AT1ARfl/fl;TH-Cre+/- (knockouts) and AT1ARfl/fl;TH-Cre-/- (controls) were used in this study. In vitro autoradiography was performed to confirm the loss of AT1AR binding from catecholaminergic cells. Telemetry devices were used to record baseline BP and heart rate (HR). For the metabolic studies, mice were housed individually in metabolic cages with free access to food and water. After 1 day acclimatization 24 hour urine output and food and water intake were recorded. Results: Binding to the AT1AR was completely absent in the adrenal medulla and thoracic sympathetic ganglia of the AT1AR fl/fl;TH-Cre+/- mice. Basal systolic BP and HR were not different between the groups (109± 1mmHg vs. 108 ± 2 mmHg and 553± 10 b.p.m vs. 573 ± 10 b.p.m). Body weight, water intake, and 24 h urine volumes were also not different between groups. Conclusion: AT1AR knockout from catecholaminergic cells does not elicit changes in metabolic state, baseline systolic BP or HR.
Funded by the Australian NHMRC