Angiotensin type 1A receptors in C1 neurons of the rostral ventrolateral medulla modulate the pressor response to aversive stress

Abstract

The rise in blood pressure during an acute aversive stress has been suggested to involve activation of angiotensin type 1A receptors (AT 1ARs) at various sites within the brain, including the rostral ventrolateral medulla. In this study we examine the involvement of AT 1ARs associated with a subclass of sympathetic premotor neurons of the rostral ventrolateral medulla, the C1 neurons. The distribution of putative AT 1AR-expressing cells was mapped throughout the brains of three transgenic mice with a bacterial artificial chromosomeexpressing green fluorescent protein under the control of theAT 1ARpromoter. The overall distribution correlated with that of theAT 1ARs mapped by other methods and demonstrated that the majority of C1 neurons express the AT 1AR. Cre-recombinase expression in C1 neurons of AT 1AR-floxed mice enabled demonstration that the pressor response to microinjection of angiotensin II into the rostral ventrolateral medulla is dependent upon expression of theAT 1ARin these neurons. Lentiviral-induced expression of wild-typeAT 1ARs in C1 neurons of global AT 1AR knock-out mice, implanted with radiotelemeter devices for recording blood pressure, modulated the pressor response to aversive stress. During prolonged cage-switch stress, expression ofAT 1ARs in C1 neurons induced a greater sustained pressor response when compared to the control viral-injected group (22±4 mmHg for AT 1AR vs 10±1 mmHg for GFP; p<0.001), which was restored toward that of the wild-type group (28±2 mmHg). This study demonstrates that AT 1AR expression by C1 neurons is essential for the pressor response to angiotensin II and that this pathway plays an important role in the pressor response to aversive stress. © 2012 the authors.