Chronic hypertension enhances the function of pre‐synaptic GABAB receptors in the NTS

Abstract

Microinjection of the GABAB receptor agonist baclofen into the NTS increases arterial pressure, heart rate and sympathetic nerve discharge. This response is enhanced in hypertension and is associated with increased post‐synaptic GABAB receptor function. We tested whether a presynaptic mechanism also contributes to the enhanced baclofen effect in hypertension. Whole‐cell recordings of NTS second‐order neurons identified by DiA labeling of aortic nerve were obtained in a brain slice from normotensive control (NT) and renal‐wrap hypertensive (HT) rats. After 4 weeks, arterial blood pressure was 162±9 mmHg in HT rats (n=6) and 107±3 mmHg in NT rats (n=6/11) (p<0.001). Baclofen reduced amplitude of evoked EPSCs (eEPSCs) elicited by tractus stimulation and the EC50 of was significantly greater in NT rats (1.5±0.5 μM, n=6) than HT rats (0.6±0.1 μM, n=6, p<0.05). Baclofen (1 μM) elicited greater inhibition of eEPSCs in HT (58±6%, n=9) than NT cells (40±6%, n=8, p<0.05). HT cells (0.60±0.08, n=8) had greater paired‐pulse ratio (PPR) of eEPSCs than NT cells (0.48±0.06, n=5, p<0.05). After application of baclofen (1 μM) HT cells (0.92±0.07) had greater PPR than NT cells (0.67±0.05, p<0.05). The results suggest that in renal‐wrap HT rats baclofen evokes an enhanced presynaptic inhibition of glutamate release in 2nd‐order baroreceptor neurons. This enhanced inhibition could alter baroreflex function in hypertension.