Abstract
P47 In renal wrap chronic hypertensive (CHT) rats, injection of the GABA B 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 GABA B 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 GABA B receptor mRNA in the NTS in CHT rats.
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