Activation of Hypothalamic AgRP and POMC Neurons Evokes Disparate Sympathetic and Cardiovascular Responses.

The arcuate nucleus of hypothalamus (ARC) plays a key role in linking peripheral metabolic status to the brain melanocortin system, which influences a wide range of physiological processes including the sympathetic nervous system and blood pressure. The importance of the activity of agouti-related peptide (AgRP)- and proopiomelanocortin (POMC)-expressing neurons, two molecularly distinct populations of ARC neurons, for metabolic regulation is well-established, but their relevance for sympathetic and cardiovascular control remain unclear. We used designer receptors exclusively activated by designer drug (DREADD) technology to study how activation of AgRP and POMC neurons affect renal sympathetic nerve traffic and blood pressure. In addition to the drastic feeding stimulatory effect, DREADD-mediated activation of AgRP, but not POMC neurons, induced acute reduction in renal sympathetic nerve activity in conscious mice. Paradoxically, however, DREADD-mediated chronic activation of AgRP neurons caused a significant increase in blood pressure specifically in inactive light phase. On the other hand, chronic activation of POMC neurons led to a significant reduction in blood pressure. These results bring new insights into a previously unappreciated role of ARC AgRP and POMC neuronal activity in autonomic and cardiovascular regulation.