Mechanistic target of rapamycin complex 1 (
mTORC1) is a molecular node that couples extracellular cues to a wide range of cellular events controlling various physiological processes. Here, we identified
mTORC1 signaling as a critical mediator of
angiotensin II (Ang II) action in the brain. In neuronal GT1-7 cells, we show that Ang II stimulates neuronal
mTORC1 signaling in an Ang II type 1 receptor-dependent manner. In mice, a single intracerebroventricular (ICV) injection or chronic sc infusion of Ang II activated
mTORC1 signaling in the subfornical organ, a critical brain region in cardiovascular control and fluid balance. Moreover, transgenic sRA mice with brain-specific overproduction of Ang II displayed increased
mTORC1 signaling in the subfornical organ. To test the functional role of brain
mTORC1 in mediating the action of Ang II, we examined the consequence of
mTORC1 inhibition with
rapamycin on Ang II-induced increase in water intake and arterial pressure. ICV pretreatment with
rapamycin blocked ICV Ang II-mediated increases in the frequency, duration, and amount of water intake but did not interfere with the pressor response evoked by Ang II. In addition, ICV delivery of
rapamycin significantly reduced
polydipsia, but not
hypertension, of sRA mice. These results demonstrate that
mTORC1 is a novel downstream pathway of Ang II type 1 receptor signaling in the brain and selectively mediates the effect of Ang II on drinking behavior.