Abstract
Objective: It is well established that angiotensin II exerts a dampening effect on the baroreflex within the nucleus tractus solitarii, the principal brainstem site for termination of baroreceptor afferents and which is densely populated with gamma-aminobutyric acid-ergic neurons and nerve terminals. The present study was designed to investigate whether local release of gamma-aminobutyric acid is involved in the effects mediated by local angiotensin II within the nucleus tractus solitarii. Design and method: In vivo microdialysis was used for measurement of extracellular glutamate and gamma-aminobutyric acid levels and for infusion of angiotensin II and other compounds within the nucleus tractus solitarii of normotensive Wistar rats. The mean arterial pressure and heart rate responses were monitored with a pressure transducer. Angiotensin II type 1 receptor selectivity was assessed using the angiotensin II type 1 receptor antagonist candesartan; the nitric oxide synthase inhibitor was used to assess the involvement of nitric oxide in the evoked responses by infusion of angiotensin II. Results: Local infusion of angiotensin II into the nucleus tractus solitarii significantly increased extracellular gamma-aminobutyric acid levels as well as mean arterial pressure. These responses were both abolished by co-infusion of either the angiotensin II type 1 receptor antagonist candesartan, or the nitric oxide synthase inhibitor, N (ω)-nitro-L-arginine methyl ester. The pressor response to angiotensin II was reversed by co-infusion with the gamma-aminobutyric acid A receptor antagonist, bicuculline. Local blockade of nitric oxide synthase decreased both, gamma-aminobutyric acid and glutamate concentrations. Conclusions: Our results suggest that the inhibitory modulation of the baroreflex by angiotensin II involves angiotensin II type 1 receptor mediated nitric oxide dependent local gamma-aminobutyric acid release within the nucleus tractus solitarii in normotensive rats. Nitric oxide produced within the nucleus tractus solitarii tonically potentiates local gamma-aminobutyric acid and glutamate release.
Published Version
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