Chronic hypertension enhances presynaptic inhibition by baclofen in the nucleus of the solitary tract

Weirong Zhang, Steve Mifflin

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The selective γ-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 EC50 of this inhibition was greater in control (1.5±0.5 μmol/L; n=6) than in hypertensive cells (0.6±0.1 μmol/L; n=9; P±0.05). Baclofen (1 μmol/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.

Original languageEnglish
Pages (from-to)481-486
Number of pages6
JournalHypertension
Volume55
Issue number2
DOIs
StatePublished - Feb 2010

Keywords

  • Baroreceptor
  • Baroreflex
  • Blood pressure
  • Cardiovascular regulation
  • Hypertension

Fingerprint Dive into the research topics of 'Chronic hypertension enhances presynaptic inhibition by baclofen in the nucleus of the solitary tract'. Together they form a unique fingerprint.

Cite this