Gabab Receptor Mediated Responses in the Nucleus Tractus Solitarius (NTS) Are Altered in Acute and Chronic Hypertensive Rats.
In renal wrap chronic hypertensive (CHT) rats, injection of the GABAB agonist baclofen into the NTS evokes a greater increase in mean arterial pressure (MAP) than in normotensive (NT) controls, and in CHT rats there is an increased expression of GABAB receptor mRNA in the NTS (Hypertension, 33:530). We report that the pressor response to injection of baclofen into the NTS is enhanced following acute hypertension (AHT) of only 30 minutes. Sprague-Dawley rats were anesthetized with Inactin (60mg/kg), paralyzed and artificially ventilated. Following unilateral electrolytic ablation of the NTS, microinjection of 40pmoles of baclofen into the contralateral NTS of NT (101±2mmHg) rats resulted in an increase in MAP of 21±1mmHg (n=7). During AHT (30 min of phenylephrine infusion, MAP increased to 135±3mmHg), microinjection of baclofen increased MAP by 34±2mmHg (n=13). This was significantly greater than the response before AHT (p<.01) and no different from the response in CHT rats (37±3mmHg, n=8, p>.80). Intravenous injections of norepinephrine (n=3) and angiotensin II (n=3) produced the same increases in MAP before and during AHT (p>.4) so the enhanced baclofen response is not due to a change in vascular reactivity. Baclofen has both pre- and post-synaptic effects. To eliminate the pre-synaptic component of the baclofen response sino-aortic denervations (SAD) were performed prior to the microinjections. In NT-SAD rats, baclofen injections increased MAP by 12±1mmHg (n=8), in AHT-SAD by 12±1mmHg (n=12)and in CHT-SAD rats by 20±3mmHg (n=7). To conclude, the pressor response to NTS injections of baclofen is enhanced in both CHT and AHT rats. The increase in baroreceptor afferent input to NTS during phenylephrine induced AHT provides a greater substrate for pre-synaptic inhibition by baclofen since the post-synaptic component of the baclofen response is the same in NT-SAD and AHT-SAD. The enhanced pressor response in CHT rats is associated with an increased post-synaptic component of the baclofen response, consistent with our previous finding of an increase in GABAB receptor mRNA in the NTS in CHT rats.