Enhanced pressor response to GABA in the nucleus tractus solitarii of the spontaneously hypertensive rat.
A previous study from this laboratory demonstrated that ongoing GABAergic neurotransmission in the nucleus tractus solitarii (NTS) functions to maintain baseline arterial pressure (AP). In that study, bilateral microinjection of nipecotic acid into the NTS was observed to elevate AP. Since nipecotic acid is a selective GABA uptake blocker, changes in GABA release should be reflected by changes in the response to nipecotic acid. The present study utilized this approach to assess endogenous GABA activity within the NTS of the spontaneously hypertensive rat (SHR). Male SHR, 16-20 weeks of age, were anesthetized with chloralose, paralyzed and ventilated. Age-matched Wistar-Kyoto (WKY) rats were studied as controls. Bilateral microinjection of nipecotic acid (10 nmol in 100 nl; a maximally effective dose) into the NTS elicited a pressor response which was significantly greater in the SHR than the response observed in the WKY rats. Similarly, direct stimulation of GABAB receptors in the NTS with (-)-baclofen 40 pmol, a maximally effective dose) elicited an increase in AP which was significantly greater in the SHR. In contrast, bilateral microinjection of the direct acting GABAA agonist muscimol (160 pmol, a maximally effective dose) resulted in a similar elevation of AP in both the SHR and WKY rats. These results suggest that the enhanced pressor response caused by endogenous GABA in the NTS of the SHR is due to a greater response evoked by stimulation of GABAB receptors. Thus, enhanced GABAB receptor-mediated neural transmission in the NTS may contribute to the expression or maintenance of hypertension in this genetic model of hypertension.
Catelli
J M
JM
Department of Behavioral Neuroscience, University of Pittsburgh, PA 15260.
Sved
A F
AF
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001933:Brain Stem / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009557:Nipecotic Acids / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D009557:Nipecotic Acids; C030278:nipecotic acid; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D011392:Proline; C010983:homoproline; D001418:Baclofen