Chronic Hypertension Enhances Presynaptic Inhibition by Baclofen in the Nucleus of the Solitary Tract

The selective gamma-aminobutyric acid B-subtype receptor agonist baclofen activates both presynaptic and postsynaptic receptors in the brain. Microinjection of baclofen into the nucleus of the solitary tract increases arterial pressure, heart rate, and sympathetic nerve discharge consistent with inhibition of the arterial baroreflex. The magnitude of these responses is enhanced in hypertension and is associated with increased postsynaptic GABA(B) receptor function. We tested whether a presynaptic mechanism contributes to the enhanced baclofen inhibition in hypertension. Whole-cell recordings of second-order baroreceptor neurons, identified by 4-(4-(dihexadecylamino) styryl)-N-methylpyridinium iodide labeling of aortic nerve, were obtained in brainstem slices from normotensive control and renal-wrap hypertensive rats. After 4 weeks, arterial blood pressure was 162 +/- 9 mm Hg in hypertensive (n=6) and 107 +/- 3 mmHg in control rats (n=6/11; P<0.001). Baclofen reduced the amplitude of excitatory postsynaptic currents evoked by solitary tract stimulation and the EC(50) of this inhibition was greater in control (1.5 +/- 0.5 mu mol/L; n=6) than in hypertensive cells (0.6 +/- 0.1 mu mol/L; n=9; P<0.05). Baclofen (1 mu mol/L) elicited greater inhibition on evoked response in hypertensive (58 +/- 6%; n=9) than in control cells (40 +/- 6%; n=8; P<0.05). Another index of presynaptic inhibition, the paired-pulse ratio (ratio of second to first evoked response amplitudes at stimulus intervals of 40 ms), was greater in hypertensive (0.60 +/- 0.08; n=8) than in control cells (0.48 +/- 0.06; n=5; P<0.05). The results suggest that in renal-wrap hypertensive rats, baclofen causes an enhanced presynaptic inhibition of glutamate release from baroreceptor afferent terminals to second-order neurons in the nucleus of the solitary tract. This enhanced presynaptic inhibition could contribute to altered baroreflex function in hypertension. (Hypertension. 2010;55[part2]:481-486.)