Alterations in 5‐HT and glutamate release in the rat NTS in heart failure (686.10)

Abstract

In man and in animal models of early heart failure the baroreflex and the cardiopulmonary reflex have been reported to be impaired. Glutamate and 5‐HT are released in the nucleus tractus solitarius (NTS) by cardiovascular afferent activation (see Ramage & Villalón, 2008, TIPS 29:472‐481). The present study was designed to determine if the release of these transmitters in real time is altered in the rat permanent‐occlusion heart failure model. 5‐HT was measured via a carbon fibre electrode using a modified form of fast differential voltammetry, while glutamate was measured using a glutamate biosensor (Sarissaprobes®). Rats, with heart failure or sham operated were anaesthetized with α‐chloralose (120 mg/kg; i.v), neuromuscular blocked and artificially ventilated. Activation of cardiopulmonary afferents by phenylbiguanide (PBG; i.a.) caused a significant (P< 0.05; n=4) increase in 5‐HT to 29 ± 6nM in heart failure compared to 10 ± 0.4nM in sham operated rats. PBG evoked a significantly smaller hypotension in heart failure (34 ± 5mmHg) compared to that of sham (58 ± 6 mmHg) rats. However, PBG evoked bradycardia was not significantly different, 148 ± 39 compared to 191 ± 12 bpm in sham rats. Activation of the depressor reflex by i.v. injection of phenylephrine (3μg per animal) caused a significantly greater increase in glutamate in heart failure (1.6 ± 0.2μM; n=3) compared to sham (0.6 ± 0.2μM, n=3) rats. The cardiovascular effects were not significantly different. In conclusion this preliminary data suggests that in heart failure afferent activation increases the release of these two transmitters in nucleus tractus solitarius (NTS). The consequence of this in the development of heart failure remains to be determined.