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(Hypertension. 2007;49:659.)
© 2007 American Heart Association, Inc.

Original Articles, Part 2

Chronic Hypertension Enhances the Postsynaptic Effect of Baclofen in the Nucleus Tractus Solitarius

From the Department of Pharmacology, University of Texas Health Science Center at San Antonio.

Correspondence to Steve W. Mifflin, Department of Pharmacology, MSC 7764, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229. E-mail mifflin{at}uthscsa.edu

Microinjection of the inhibitory neurotransmitter -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 G) 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 -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.

Key Words: cardiovasular regulation • baroreceptor • baroreflex • hypertension • blood pressure

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