gamma-Aminobutyric acid(B) receptor-mediated responses in the nucleus tractus solitarius are altered in acute and chronic hypertension.
The increase in mean arterial pressure evoked by injection of the gamma-aminobutyric acid (GABA)(B) agonist baclofen into the nucleus tractus solitarius (NTS) is greater in spontaneously hypertensive rats and renal wrap chronically hypertensive (CHT) rats compared with normotensive (NT) controls. We report here that the baclofen-induced pressor response (BIPR) is enhanced after acute hypertension (AHT) of only 30 minutes. Sprague-Dawley rats were anesthetized with Inactin, paralyzed, and artificially ventilated. As we previously reported, after unilateral electrolytic ablation of the NTS, microinjection of 40 pmol baclofen into the contralateral NTS of NT rats resulted in a BIPR of 22+/-1 mm Hg (n=12). During the infusion of phenylephrine for 30 minutes (AHT), the BIPR was 39+/-5 mm Hg (n=10), significantly greater than the response in NT rats (P<0.01) and no different from the response in CHT rats (39+/-5 mm Hg, n=7). Baclofen has both presynaptic and postsynaptic effects. To eliminate the presynaptic component of the baclofen response, sinoaortic denervation (SAD) was performed before the microinjections. The magnitude of the BIPR was 12+/-1 mm Hg in NT-SAD rats (n=8), 12+/-1 mm Hg in AHT-SAD rats (n=12), and 20+/-3 mm Hg in CHT-SAD rats (n=7). The BIPR is enhanced in both CHT and AHT rats. It appears that the increase in baroreceptor afferent input to NTS during phenylephrine-induced AHT provides a greater substrate for presynaptic inhibition by baclofen because the postsynaptic component of the baclofen response is the same in NT-SAD and AHT-SAD. The enhanced BIPR in CHT rats appears to be associated with an enhancement of both the presynaptic and postsynaptic components of the response.
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, Texas, USA.
M
M
Vitela
S W
SW
Mifflin
D000208:Acute Disease; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D003714:Denervation; D018755:GABA Agonists / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000378:metabolism*; D017552:Solitary Nucleus / Q000378:metabolism*; D014628:Vagotomy
D018755:GABA Agonists; D018080:Receptors, GABA-B; D010656:Phenylephrine; D001418:Baclofen; D009638:Norepinephrine