Role of Chemoreceptor Activation in Hemodynamic Responses to Electrical Stimulation of the Carotid Sinus in Conscious Rats

Abstract

Electrical carotid baroreflex activation has been used to treat patients with resistant hypertension. It is hypothesized that, in conscious rats, combined activation of carotid baro- and chemoreceptors afferences attenuates the reflex hypotension. Rats were divided into 4 groups: 1) control group, with unilateral denervation of the right carotid chemoreceptors; 2) chemoreceptor denervation group, with bilateral ligation of the carotid body artery; 3) baroreceptor denervation group, with unilateral denervation of the left carotid baroreceptors and right carotid chemoreceptors; 4) carotid bifurcation denervation group, with denervation of the left carotid baroreceptors and chemoreceptors, plus denervation of the right carotid chemoreceptors. Animals were subjected to 4 rounds of electrical stimulation (5 V, 1 ms), with 15 Hz, 30 Hz, 60 Hz, and 90 Hz applied randomly for 20 s. Electrical stimulation caused greater hypotensive responses in the chemoreceptor denervation group than in the control group, at 60 Hz (−37 mmHg vs −19 mmHg) and 90 Hz (−33 mmHg vs −19 mmHg). The baroreceptor denervation group showed hypertensive responses at all frequencies of stimulation. In contrast, the carotid sinus denervation group showed no hemodynamic responses. The control group presented no changes in heart rate, whereas the chemoreceptor denervation group and the baroreceptor denervation group showed bradycardic responses. These data demonstrate that carotid chemoreceptor activation attenuates the reflex hypotension caused by combined electrical stimulation of the carotid sinus and the carotid sinus nerve in conscious rats. These findings may provide useful insight for clinical studies using Baroreflex Activation Therapy in resistant hypertension and/or heart failure.

Chronic Interactions Between Carotid Baroreceptors and Chemoreceptors in Obesity Hypertension

“…This suggests that the long-term antagonism between the baroreceptors and chemoreceptors on ventilation occurs only at heightened levels of chemoreceptor activation. In this regard it is relevant that activation of carotid chemoreceptor afferent fibers by electrical stimulation of the carotid sinus nerve may increase respiration and arterial pressure, 36–38 changes opposite to those observed during carotid sinus stimulation in the obese dogs in the present study. However, despite carotid body afferents being in close proximity to carotid baroreceptors, there are no clinically relevant respiratory changes in hypertensive subjects with normal minute ventilation during electrical stimulation of the carotid sinus at intensities that reduce arterial pressure.…”

“…Furthermore, in the context of the present study identifying increased peripheral chemoreflex activation as a stimulus that contributes to obesity hypertension, these findings are consistent with the hypothesis that one component of sustained baroreflex-mediated sympathoinhibition includes reduced chemoreceptor-mediated sympathoexcitatory drive through the central interactions of these reflexes. 35–36 It is also possible that baroreflex activation may diminish the tonic excitatory effects of peripheral chemoreceptor activity in obesity by reducing sympathetic tone to the arterioles perfusing the carotid bodies. This would increase blood flow and suppress chemoreceptor activation by raising PaO 2 locally in the vicinity of the glomus cells or by reducing carotid body hyperactivity by other flow dependent mechanisms.…”

Selective denervation of the aortic and carotid baroreceptors in rats

“…Furthermore, activation of the peripheral chemoreceptors produced increases in carotid sinus nerve discharges in both SHAM and BARO-X groups. Thus, the hypertensive and bradycardic Using the technique described in the present study, our group demonstrated the role played by the carotid chemoreceptors in the haemodynamic (arterial pressure and heart rate) responses to electrical stimulation of the left carotid sinus in conscious rats (Katayama et al, 2015). These authors assessed the relative role of the carotid chemoreceptors by means of selective denervation of the left carotid baroreceptors, maintaining the integrity of the carotid chemoreceptors.…”

“…However, in the study by Katayama et al. (), because the right carotid baroreceptors and aortic baroreceptors on both sides were kept intact, the efficacy of the selective baroreceptor denervation was based on the lack of haemodynamic responses to progressive changes in pressure of the isolated left carotid sinus. Importantly, recent studies have proposed that the carotid body chemoreceptors are involved in the pathophysiology of cardiovascular, respiratory and metabolic diseases (Abdala et al., ; Del Rio et al., ; Marcus et al., ; Paton et al., ; Prabhakar, ; Ribeiro et al., ; Schultz et al., ) showing, from the translational point of view, the importance of studying the individual roles of these receptors.…”

“…These authors assessed the relative role of the carotid chemoreceptors by means of selective denervation of the left carotid baroreceptors, maintaining the integrity of the carotid chemoreceptors. However, in the study by Katayama et al (2015), because the right carotid baroreceptors and aortic baroreceptors on both sides were kept intact, the efficacy of the selective baroreceptor denervation was based on the lack of haemodynamic responses to progressive changes in pressure of the isolated left carotid sinus.…”