Physical (in)activity‐induced changes in tonic excitation and inhibition in the rostral ventrolateral medulla (686.37)

Abstract

The RVLM contains neurons that regulate blood pressure and exhibit (in)activity‐dependent neuroplasticity. Previous studies have found that sedentary animals have enhanced responses to direct activation of RVLM neurons that regulate sympathetic nervous activity (SNA). We hypothesized that sedentary animals have heightened sympathoexcitation due to enhanced glutamatergic and/or attenuated GABAergic neurotransmission. Rats were housed with or without running wheels for 12 weeks and were then anesthetized with Inactin and instrumented to record mean arterial pressure, heart rate, and splanchnic SNA during microinjections into the RVLM. The RVLM was functionally identified by a pressor response to glutamate (30 nl, 100 mM). Bilateral blockade of GABAA receptors with bicuculline (5mM) was performed either alone or following bilateral injection of the ionotropic glutamate receptor antagonist kynurenic acid (40 mM). Sedentary versus active rats displayed a greater SNA response following bicuculline injection alone (Δ62±7% v Δ38±8%, p<0.05). The SNA response to bicuculline after injection of kynurenate was attenuated in sedentary rats (Δ62%±7 v Δ 26%±4, p<0.05). Active rats did not show a significant SNA attenuation (Δ38±8% v Δ31±6%, p>0.05). These findings suggest that the exaggerated SNA increase in sedentary versus physically active rats following GABAA blockade is mediated by enhanced activation of ionotropic glutamate receptors. This study further demonstrates (in)activity‐dependent alterations in the RVLM and these changes may contribute to an increased risk for cardiovascular disease in sedentary individuals.Grant Funding Source: Supported by R01‐HL096787