Chronic hypertension enhances the postsynaptic effect of baclofen in the nucleus tractus solitarius.
Microinjection of the inhibitory neurotransmitter gamma-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 GOmega) between hypertensive and normotensive neurons (both n=18). Baclofen induced a net outward current in nucleus tractus solitarius neurons in the presence of 1 micromol/L tetrodotoxin. The EC50 of the baclofen effect was greater in normotensive cells (9.1+/-3.2 micromol/L; n=5) than hypertensive cells (3.0+/-0.5 micromol/L; n=7; P<0.05), and baclofen (10 micromol/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 gamma-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.
Zhang
Weirong
W
Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Herrera-Rosales
Myrna
M
Mifflin
Steve
S
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D018755:GABA Agonists / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000187:drug effects; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D018755:GABA Agonists; D001418:Baclofen