Abstract 278: Down-Regulation of Corticosterone Actions Within Nucleus of the Solitary Tract Catecholaminergic Neurons Attenuates Cardiovascular Responses to Stress
We previously reported that chronic increases in corticosterone within the dorsal hindbrain, including the Nuclues of the Solitary Tract (NTS), augment the arterial pressure response to restraint stress. This study tested the hypothesis that diminishing actions of corticosterone selectively within NTS catecholaminergic neurons would attenuate the cardiovascular responses to novel and repeated restraint stress. AAV2-based viral vectors were constructed to express either GFP or 11-beta-hydroxysteroid dehydrogenase 2 (HSD2) selectively in catecholaminergic neurons using the PRSx8 promoter. HSD2 degrades corticosterone to an inactive metabolite. Adult male Sprague-Dawley rats were instrumented with telemetry mitters to measure arterial pressure and heart rate. At least 3 weeks later AAV2-PRSx8-HSD2 (n=7) or AAV2-PRSx8-eGFP (n=8) was microinjected bilaterally into the NTS (125 nl/side). After another 3 weeks rats underwent daily restraint stress (60 min per day) for 15 days. Baseline mean arterial pressure was not significantly different in GFP- versus HSD2-transduced rats prior to stress 1 (98±2 and 99±3 mmHg respectively) or stress 15 (96±3 and 100±2 mmHg respectively). During the first restraint stress, the average increase in arterial pressure in response to restraint was significantly (P<0.05) greater in the GFP- compared with the HSD2-transduced rats during the final 10 min of stress (13±1 and 5±2 mmHg respectively). During the last restraint stress the average increase in arterial pressure in response to stress was significantly (P<0.05) greater in the GFP- compared with the HSD2- transduced rats throughout the stress (11±2 and 4±1 mmHg respectively). Baseline heart rate was significantly higher in GFP- versus HSD2- transduced rats prior to stress 1 (340±6 and 317±7 bpm respectively) but not prior to stress 15 (308±6 and 309±9 bpm respectively). HSD2 transduction had no significant effect on the heart rate response to the first stress, but significantly reduced the average heart rate response to the last restraint stress (63±13 and 30±7 bpm for GFP vs HSD2). We conclude that over-expression of HSD2 in NTS catecholaminergic neurons lowers baseline heart rate and attenuates the cardiovascular responses to restraint stress.
- © 2012 by American Heart Association, Inc.