In hypertension, activation of the skeletal muscle EPR elicits an exaggerated blood pressure (BP) response. Neural input from the EPR is processed within the NTS of the brainstem. Normally, NO produced within the NTS buffers the BP response to EPR activation. Thus, we hypothesized that EPR overactivity in hypertension is mediated by a decrease in NO production within the NTS. To test this hypothesis, NO production within the NTS was assessed during stimulation of the EPR in normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Diaminoanthraquinone (DAA), an immunofluorescent molecule that irreversibly binds to NO, was dialyzed into the NTS. The integrated density of DAA fluorescence is directly related to the production of NO. Basal NO production (F0) was measured in WKY and SHR. In separate animals, the EPR was stimulated intermittently for 15 min by electrically‐inducing hindlimb muscle contraction. During this 15 min period, DAA was concomitantly dialyzed into the NTS and subsequently measured (F1). The F1/F0 ratio was used to evaluate NO production during muscle contraction. DAA fluorescence was greater in WKY than SHR after EPR activation (WKY F1/F0 5.8 ± 1.4 A.U.; SHR F1/F01.9 ± 0.7 A.U.;p<0.01). The data suggest that NO production is reduced within the NTS of SHR during muscle contraction and likely contributes to the EPR overactivity manifest in hypertension. Supported by NIH HL‐088422.