Attenuated baroreflex control of sympathetic nerve activity in obese Zucker rats by central mechanisms

Abstract

Adult obese Zucker rats (OZRs) have reduced sympathetic responses to evoked changes in arterial pressure (AP) compared to lean Zucker rats (LZRs). This study examined whether attenuated sympathetic baroreflexes in OZRs may be due to altered sensory or central mechanisms. The OZRs had elevated baseline splanchnic sympathetic nerve activity (SNA) and mean AP (MAP) compared to age-matched LZRs under urethane anaesthesia (P < 0.05). Aortic depressor nerve activity (ADNA) was measured while AP was altered by infusions of phenylephrine or nitroprusside (+/-60 mmHg over 60-90 s) in rats treated with atropine and propranolol to eliminate changes in heart rate. Although baseline ADNA was higher in the hypertensive OZRs, the relationship between MAP and ADNA was comparable in OZRs and LZRs. In contrast, electrical stimulation of the ADN afferent fibres (5 s train, 2 ms pulses, 4 V, 0.5-48 Hz) produced dramatically smaller reductions in SNA and MAP in OZRs compared to LZRs (P < 0.05). After blockade of alpha-adrenergic receptors to prevent sympathetically mediated depressor responses, OZRs still had reduced sympathetic responses to stimulation of the ADN. In addition, stimulation of vagal afferent nerves electrically or with phenylbiguanide (1, 2, 4 and 8 microg, i.v.) produced smaller inhibitions of SNA in OZRs compared with LZRs (P < 0.05). These data suggest that attenuated sympathetic baroreflexes are the result of altered central mechanisms in OZRs, and not deficits in the responsiveness of aortic baroreceptors to AP. Furthermore, central deficits in the regulation of SNA in OZRs extend to other sympathoinhibitory reflexes initiated by vagal afferent nerves.