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Development of attenuated baroreflexes in obese Zucker rats coincides with impaired activation of nucleus tractus solitarius

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AJP Regulatory Integrative and Comparative Physiology

Published online on

Abstract

Adult obese Zucker rats (OZR; >12 wks) develop elevated sympathetic nerve activity (SNA) and mean arterial pressure (MAP) with impaired baroreflexes compared to adult lean Zucker rats (LZR) and juvenile OZR (6-7 wks). In adult OZR, baroreceptor afferent nerves respond normally to changes in MAP, whereas electrical stimulation of baroreceptor afferent fibers produces smaller reductions in SNA and MAP compared to LZR. We hypothesized that impaired baroreflexes in OZR are linked to reduced activation of brainstem sites that mediate baroreflexes. In conscious adult rats a hydralazine (HDZ)-induced reduction in MAP evoked tachycardia that was initially blunted in OZR, but equivalent to LZR within 5 minutes. In agreement, HDZ-induced expression of c-Fos in the rostral ventrolateral medulla (RVLM) was comparable between groups. In contrast, phenylephrine (PE)-induced rise in MAP evoked markedly attenuated bradycardia with dramatically reduced c-Fos expression in nucleus tractus solitarius (NTS) of adult OZR compared to LZR. However, in juvenile rats PE-induced hypertension evoked comparable bradycardia in OZR and LZR with similar or augmented c-Fos expression in NTS of the OZR. In urethane-anesthetized rats, microinjections of glutamate into NTS evoked equivalent decreases in SNA, HR, and MAP in juvenile OZR and LZR, but attenuated decreases in SNA and MAP in adult OZR. In contrast, microinjections of glutamate into the caudal ventrolateral medulla, a target of barosensitive NTS neurons, evoked comparable decreases in SNA, HR, and MAP in adult OZR and LZR. These data suggest OZR develop impaired glutamatergic activation of the NTS that likely contributes to attenuated baroreflexes in adult OZR.