Diet-induced obesity severely impairs myelinated aortic baroreceptor reflex responses

Abstract

Diet-induced obesity (DIO) attenuates the arterial cardiac baroreceptor reflex, but the mechanisms and sites of action are unknown. This study tested the hypothesis that DIO impairs central aortic baroreceptor pathways. Normal chow control (CON) and high-fat-chow obesity-resistant (OR) and obesity-prone (OP) rats were anesthetized (inactin, 120 mg/kg) and underwent sinoaortic denervation. The central end of the aortic depressor nerve (ADN) was electrically stimulated to generate frequency-dependent baroreflex curves (5-100 Hz) during selective activation of myelinated (A-fiber) or combined (A- and C-fiber) ADN baroreceptors. A mild stimulus (1 V) that activates only A-fiber ADN baroreceptors induced robust, frequency-dependent depressor and bradycardic responses in CON and OR rats, but these responses were completely abolished in OP rats. Maximal activation of A fibers (3 V) elicited frequency-dependent reflexes in all groups, but a dramatic deficit was still present in OP rats. Activation of all ADN baroreceptors (20 V) evoked even larger reflex responses. Depressor responses were nearly identical among groups, but OP rats still exhibited attenuated bradycardia. In separate groups of rats, the reduced heart rate (HR) response to maximal activation of ADN A fibers (3 V) persisted in OP rats following pharmacological blockade of β(1)-adrenergic or muscarinic receptors, suggesting deficits in both parasympathetic nervous system (PNS) and sympathetic nervous system (SNS) reflex pathways. However, the bradycardic responses to direct efferent vagal stimulation were similar among groups. Taken together, our data suggest that DIO severely impairs the central processing of myelinated aortic baroreceptor control of HR, including both PNS and SNS components.

Fig. 1.

A: representative arterial pressure (AP) and heart rate (HR) tracings show that the activation of myelinated aortic depressor nerve (ADN) baroreceptors (1 V, 100 Hz) evoked similarly robust reflex responses in a control (CON) and obesity-resistant (OR) rat, whereas these responses are completely absent in an obesity-prone (OP) rat. B: group data show that activation of myelinated ADN baroreceptors (1 V stimulus) evokes frequency-dependent depressor (top) and bradycardic (bottom) responses between 20 and 100 Hz in CON (n = 5) and OR (n = 5) rats, with no difference between groups. OP rats (n = 6) exhibited no significant responses at any stimulation. bpm, Beats/min. *P < 0.05 vs. CON; †P < 0.05 vs. OR.

Fig. 2.

A: representative AP and HR tracings show that the activation of all myelinated and some unmyelinated ADN baroreceptors (3 V, 100 Hz) evoked similarly robust reflex responses in a CON and OR rat. Although these responses were also present in the OP rat, the magnitude is clearly impaired. B: group data show that activation of all myelinated baroreceptors (3 V) evokes frequency-dependent depressor (top) and bradycardic (bottom) responses between 10 and 100 Hz in CON (n = 5) and OR (n = 5) and OP (n = 6) rats, although responses were highly attenuated in OP rats compared with OR and CON rats. Again, there was no difference in reflex responses between CON and OR rats. *P < 0.05 vs. CON; †P < 0.05 vs. OR.

Fig. 3.

A: representative AP and HR tracings show that the activation of all myelinated and unmyelinated ADN baroreceptors (20 V, 100 Hz) evokes robust reflex responses in CON, OR, and OP rats. The depressor response was preserved in the OP rat, although the magnitude of the bradycardia was still clearly impaired. B: group data show that activation of all ADN baroreceptor afferents evoked frequency-dependent depressor (graph on top) and bradycardic (graph on bottom) responses between 5 and 100 Hz in CON (n = 5) and OR (n = 5) and OP (n = 6) rats. The magnitude of the depressor responses was similar between groups, but the fall in HR was still greatly attenuated in OP rats compared with OR and CON rats. There was no difference in reflex responses between CON and OR rats. *P < 0.05 vs. CON; ^†P < 0.05 vs. OR.

Fig. 4.

Similar to protocol 1, OP rats exhibited impaired depressor and bradycardic responses compared with CON and OR (P < 0.05). During the activation of all myelinated ADN baroreceptors (3 V), blockade of β₁-adrenergic receptors with atenolol had no effect on the depressor responses (A) in any group, but the bradycardic response (B) was reduced in CON and OR rats but not in OP rats. #P < 0.05 vs. pre-atenolol; *P < 0.05, OP vs. CON; †P < 0.05 OP vs. OR.

Fig. 5.

Similar to protocol 1, OP rats exhibited impaired depressor and bradycardic responses compared with CON and OR rats (P < 0.05). During the activation of all myelinated ADN baroreceptors (3 V), muscarinic blockade with methscopolamine had no effect on the depressor responses (A) in any group. The bradycardic response (B) was reduced in CON and OR rats but not in OP rats. #P < 0.05 vs. pre-methscopolamine; *P < 0.05 OP vs. CON; †P < 0.05 OP vs. OR.

Fig. 6.

The contribution of the parasympathetic nervous system (PNS, A) and the sympathetic nervous system (SNS, B) to the bradycardic response during 3 V ADN stimulation during the activation of all myelinated ADN baroreceptors is varied between CON, OR, and OP rats. Although the total reflex bradycardia during activation of ADN baroreceptors is similar between CON and OR rats, CON rats are more reliant on SNS withdrawal to lower HR, whereas OR rats are more reliant on the activation of PNS pathways. When compared with both CON and OR rats at the same time, the overall attenuated reflex bradycardia in OP rats is clearly attributed to both attenuated contributions of PNS activation and SNS withdrawal. *P < 0.05 CON vs. OP; †P < 0.05 OR vs. OP, ‡P < 0.05 CON vs. OR.

Fig. 7.

The bradycardic response to efferent vagal stimulation was not different between CON, OR, and OP rats.