Chronic hypertension enhances the postsynaptic effect of baclofen in the nucleus tractus solitarius

Weirong Zhang, Myrna Herrera-Rosales, Steve Mifflin

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Microinjection of the inhibitory neurotransmitter γ-aminobutyric acid B-subtype receptor agonist baclofen into the nucleus tractus solitarius increases arterial blood pressure and sympathetic nerve discharge. The baclofen-induced pressor response is enhanced in chronic hypertension. We hypothesized that a postsynaptic mechanism contributes to the enhanced responses to baclofen in hypertension. We investigated the postsynaptic effect of baclofen on second-order baroreceptor neurons, identified by 1,1′-dilinoleyl-3,3,3′,3′-tetra-methylindocarbocyanine, 4-chlorobenzenesulphonate labeling of the aortic nerve, in nucleus tractus solitarius slices from sham-operated normotensive and unilateral nephrectomized, renal-wrap hypertensive rats. After 4 weeks, arterial blood pressure was 153±7 mm Hg in hypertensive rats (n=9) and 93±3 mm Hg in normotensive rats (n=8; P<0.05). There was no difference in resting membrane potential (54.5±0.7 versus 53.3±0.6 mV) or input resistance (1.07±0.11 versus 1.03±0.11 GΩ) between hypertensive and normotensive neurons (both n=18). Baclofen induced a net outward current in nucleus tractus solitarius neurons in the presence of 1 μmol/L tetrodotoxin. The EC50 of the baclofen effect was greater in normotensive cells (9.1±3.2 μmol/L; n=5) than hypertensive cells (3.0±0.5 μmol/L; n=7; P<0.05), and baclofen (10 μmol/L) induced a greater decrease in input resistance in hypertensive cells (61±2%; n=6) than in normotensive cells (45±4%; n=9; P<0.05). Both potassium and calcium channels were involved in the baclofen-evoked whole-cell current. The results suggest an enhanced postsynaptic response to activation of inhibitory neurotransmitter γ-aminobutyric acid B-subtype receptors in second-order baroreceptor neurons in the nucleus tractus solitarius in renal-wrap hypertensive rats. This enhanced inhibition could alter baroreflex function in chronic hypertension.

Original languageEnglish
Pages (from-to)659-663
Number of pages5
JournalHypertension
Volume49
Issue number3 PART 2 SUPPL.
DOIs
StatePublished - 1 Mar 2007

Keywords

  • Baroreceptor
  • Baroreflex
  • Blood pressure
  • Cardiovasular regulation
  • Hypertension

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