S7.2 Altered autonomic control of cardiovascular function in obesity: Insights from obese Zucker rats

Abstract

Human obesity is associated with the development of hypertension and exaggerated cardiovascular responses to stress. Underlying these attributes are elevated sympathetic nerve activity (SNA) and impaired baroreflexes. To begin to determine mechanisms underlying obesity-associated deficits in autonomic control we studied obese Zucker rats (OZR), which are hyperphagic due to a mutated leptin receptor. Compared to lean Zucker rats (LZR), which have functional leptin receptors, the OZR become obese shortly after weaning and develop autonomic deficits as they approach adulthood. Adult OZR have elevated arterial pressure (AP) and SNA compared to LZR. In addition, OZR have exaggerated sympatho-excitatory responses (somatic and diving reflexes) but blunted sympathetic baroreflexes compared to LZR. The following studies were performed in adult OZR and LZR (14–16 wks old) that were anesthetized with urethane (1.7 g/kg LZR weight, iv), ventilated, and paralyzed. Direct recordings of baroreceptor afferent nerve activity (aortic depressor nerve, ADN) showed that ADN responses to evoked changes in AP were comparable in OZR and LZR. In contrast, electrical stimulation of the ADN evoked blunted inhibitions of SNA and AP in OZR compared to LZR. This deficit appears to extend to other sympatho-inhibitory reflexes initiated by the vagus nerve, because stimulation of the vagal afferents (electrical or by iv injection of phenybiguanide, 1–16 µg) elicited smaller decreases in SNA in OZR compared to LZR. These data suggest that impaired baroreflexes in OZR are not due to the ability to sense changes in AP, but altered central mechanisms that regulate SNA.