Cardiovascular responses and neurotransmitter changes during blockade of angiotensin II receptors within the ventrolateral medulla

Abstract

Angiotensin II (Ang II) receptors are located in different regions of the brain, particularly within the cardiovascular control centers in the brainstem. These Ang II receptors are divided into AT1 and AT2 subtypes. We investigated the role of AT1 receptor subtype within the rostral (RVLM) and caudal (CVLM) ventrolateral medulla on cardiovascular responses and glutamate/GABA neurotransmission during static exercise using microdialysis in anesthetized rats. Bilateral microdialysis of a selective AT1 receptor antagonist, ZD7155 (10 μM), for 30 min into the RVLM attenuated increases in mean arterial pressure (MAP) and heart rate (HR) during a static muscle contraction. Glutamate concentrations within the RVLM decreased while GABA levels increased simultaneously during the contraction period when compared to those before ZD7155. After 60 min of discontinuation of ZD7155, MAP, HR, glutamate, and GABA levels in response to another muscle contraction returned to baseline levels. Conversely, bilateral microdialysis of ZD7155 into the CVLM potentiated cardiovascular responses during a static muscle contraction; glutamate concentrations increased while GABA levels within the CVLM decreased. All responses recovered after 60 min of discontinuation of ZD7155. These results demonstrate that medullary AT1 receptors play an important role in modulating both neurotransmission and cardiovascular function during static exercise.