Altered regulation of sympathetic nerve activity and arterial pressure by the rostral ventrolateral medulla in obese Zucker rats

Abstract

Adult obese Zucker rats (OZR) have elevated sympathetic nerve activity (SNA) and arterial pressure (AP) with blunted baroreflexes compared to lean Zucker rats (LZR). In addition, sympatho-excitatory reflexes mediated by glutamatergic activation of the rostral ventrolateral medulla (RVLM) are exaggerated in OZR. In contrast, in juvenile OZR, although sympatho-excitatory responses appear to be exaggerated, baseline AP and baroreflexes are comparable to those observed in LZR. We examined the hypothesis that glutamatergic activation of the RVLM would yield exaggerated increases in sympathetic nerve activity (SNA) in juvenile and adult OZR. Furthermore, we determined whether the increased SNA and AP observed in adult OZR could be explained by an enhanced drive from the RVLM. In urethane-anesthetized, ventilated rats microinjection of glutamate (1nmol) increased SNA and AP more in both juvenile (7 wks) and adult (14 wks) OZR compared to age-matched LZR (n=8/group, P <0.05). In adult OZR bilateral inhibition of the RVLM with muscimol (100 pmol) virtually eliminated SNA (>85%) and produced a larger decrease in AP compared to adult LZR (P <0.05). In contrast, in juvenile rats inhibition of the RVLM produced comparable decreases in AP in OZR and LZR. These data suggest that exaggerated sympatho-excitatory reflexes may be due to enhanced excitability of the RVLM in juvenile and adult OZR. In addition the increased baseline AP in adult OZR is associated with an enhanced drive from the RVLM that is not present in juvenile OZR. Support NIH HL075174 to AMS.