Median Preoptic AT1a Receptor Knockdown Does Not Diminish Drinking in Response to Peripheral Angiotensin II Administration

Thirst is an essential mechanism for organisms to maintain body fluid homeostasis and is therefore tightly regulated. Angiotensin II (Ang II) has long been known to stimulate thirst by both by its action peripherally as a circulating hormone, and centrally acting as a peptide neurotransmitter. Peripherally circulating Ang II can elicit thirst by stimulating the Subfornical Organ (SFO), which in turn stimulates other hypothalamic nuclei regulating body fluid homeostasis such as the Median Preoptic Nucleus (MnPO) presumably through Ang II signaling. Central Ang II administered via intracerebroventricular (ICV) infusion also induces thirst by directly stimulating regions such as the MnPO. Previous studies have shown that lesions of the MnPO block drinking responses to peripheral or ICV Ang II while lesions of the SFO decrease drinking stimulated by peripheral Ang II but not ICV Ang II. Based on these observations, it has been hypothesized that Ang II receptors in the MnPO are critical for drinking responses to centrally or peripherally administered Ang II. We tested this hypothesis by microinjecting an adeno‐associated virus with short hairpin RNA matched to the Angiotensin Type 1a receptor (AT1aR) into the MnPO and testing the rats for drinking responses elicited by peripheral or centrally administered Ang II. Sprague Dawley rats were separated into subcutaneous (SC) and ICV Ang II administration groups. The SC group was pretested for their drinking response to 2 mg/kg Ang II, and those animals that drank in response to the SC Ang II administration were utilized in the study. All animals were injected with the shAt1aR virus or a control virus on Day 0, and were allowed to recover before drinking tests on day 14 and day 18. ICV animals were microinjected with the viruses on Day 0 and instrumented with a chronic lateral ventricle cannula. These animals were tested for drinking responses to 2 ng Ang II in 1ul aCSF 14 and 18 days later. Unexpectedly, we found that knockdown of AT1aR in the MnPO did not reduce drinking in response to SC Ang II (p>.05), but did significantly reduce drinking in response to ICV Ang II (P<.05). These results suggest that AT1aRs in MnPO are necessary for drinking responses following ICV Ang II but not SC Ang II. It is possible that drinking responses to peripheral Ang II involves co‐transmitters, such as glutamate, in the MnPO that produce drinking in the absence of AT1aRs or that other Ang II receptors mediate this response. Support or Funding Information R01 HL119458 P01 HL088052