Interaction of baroreceptor and chemoreceptor reflex control of sympathetic nerve activity in normal humans. V K Somers, … , A L Mark, F M Abboud J Clin Invest. 1991;87(6):1953-1957. https://doi.org/10.1172/JCI115221. Research Article Animal studies have demonstrated that activation of the baroreflex by increases in arterial pressure inhibits cardiovascular and ventilatory responses to activation of peripheral chemoreceptors (PC) with hypoxia. In this study, we examined the influences of baroreflex activation on the sympathetic response to stimulation of PC and central chemoreceptors in humans. PC were stimulated by hypoxia (10% O2/90% N2) (n = 6) and central chemoreceptors by hypercapnia (7% CO2/93% O2) (n = 6). Responses to a cold pressor stimulus were also obtained as an internal reflex control to determine the selectivity of the interactive influence of baroreflex activation. Baroreflex activation was achieved by raising mean blood pressure by greater than 10 mmHg with intravenous infusion of phenylephrine (PE). Sympathetic nerve activity (SNA) to muscle was recorded from a peroneal nerve (microneurography). During hypoxia alone, SNA increased from 255 +/- 92 to 354 +/- 107 U/min (P less than 0.05). During PE alone, mean blood pressure increased and SNA decreased to 87 +/- 45 U/min (P less than 0.05). With hypoxia during baroreflex activation with PE, SNA did not increase (50 +/- 23 U/min). During hypercapnia alone, SNA increased from 116 +/- 39 to 234 +/- 72 U/min (P less than 0.01). Hypercapnia during baroreflex activation with PE increased SNA from 32 +/- 25 U/min during PE alone to 61 +/- 26 […] Find the latest version: https://jci.me/115221/pdf Interaction of Baroreceptor and Chemoreceptor Reflex Control of Sympathetic Nerve Activity in Normal Humans Virend K. Somers, Allyn L. Mark, and Francois M. Abboud Departments ofInternal Medicine and Physiology and Biophysics, Cardiovascular Center, University ofIowa, and the Veterans Administration Medical Center, Iowa City, Iowa 55242 Abstract interactions ofthese reflexes have only been studied in animals. Animal studies have demonstrated that activation of the Heistad et al. have shown in dogs that baroreflex activation barore- inhibits and flex by increases in arterial pressure inhibits cardiovascular deactivation augments the ventilatory response to and ventilatory responses to activation of chemore- stimulation of the peripheral chemoreceptors (5). In addition, peripheral Mancia et ceptors (PC) with hypoxia. In this study, we examined the influ- al. have demonstrated that vasoconstrictor re- ences of baroreflex activation on the sympathetic response to sponses to peripheral chemoreceptor stimulation are inhibited stimulation of PC and central in humans. by elevation of blood pressure and activation of baroreceptor chemoreceptors PC reflexes were stimulated by hypoxia (10% 02/90% N2) (n = and cen- (6). 6) It has been difficult to tral chemoreceptors by hypercapnia (7% C02/93% 02) (n = 6). study the interaction of baroreceptor Responses to a cold pressor stimulus were also obtained as an and chemoreceptor reflexes in humans using measurements of internal reflex control to determine the selectivity of the inter- vascular resistance and arterial pressure because the stimuli to active influence of baroreflex activation. Baroreflex activation these reflexes (vasoactive drugs and hypoxia) produce direct was achieved by raising mean blood pressure by > 10 mmHg and confounding effects on the circulation. However, with the with intravenous infusion of phenylephrine (PE). Sympathetic use of microneurographic recordings of sympathetic nerve ac- nerve activity (SNA) to muscle was recorded from a peroneal tivity (SNA),' it is feasible to study the interaction of these nerve (microneurography). During hypoxia alone, SNA in- reflexes in normal humans. We have shown that both hypoxia creased from 255±92 to 354±107 U/min (P < 0.05). During (peripheral chemoreceptor stimulation [7, 8]) and hypercapnia PE alone, mean blood pressure increased and SNA decreased (primarily central chemoreceptor stimulation [9, 10]) trigger to 87±45 U/min (P < With baroreflex increases in SNA in humans (4). Furthermore, baroreflex acti- 0.05). hypoxia during vation inhibits SNA. activation with PE, SNA did not increase (50±23 U/min). Dur- We, therefore, examined the effect ofbaro- ing hypercapnia alone, SNA increased from 116±39 to 234±72 reflex activation (elevation of systemic pressure using intrave- U/min (P < 0.01). Hypercapnia during baroreflex activation nous phenylephrine infusions) on sympathetic nerve responses with PE increased SNA from 32±25 U/min during PE alone to to stimulation of peripheral chemoreceptors (by hypoxia), to 61±26 U/min during hypercapnia and PE (P < 0.05). Like stimulation of central chemoreceptors (by hypercapnia), and to hypercapnia (but unlike hypoxia) the cold pressor test also in- a cold pressor stimulus (used as an internal reflex control). creased SNA during PE. We conclude that baroreflex activa- tion selectively abolishes the SNA response to hypoxia but not Methods to hypercapnia or the cold pressor test. The inhibitory interac- 10 normal human volunteers (7 male, 3 female) aged 24±3 yr were tion of the baroreflex and the peripheral chemoreflex may be studied. All were nonsmokers and receiving no medication. Measure- explained by convergence of baroreceptor and peripheral che- ments were taken of heart rate (EKG), breathing patterns (pneumo- moreceptor afferents on neurons in the medulla. (J. Clin. In- tach), blood pressure (Physio-Control Lifestat 200 semiautomated vest. 1991. 87:1953-1957.) Key words: hypoxia - hypercapnia. sphygmomanometer; Redmond, WA), 02 saturation (Nellcor N-l 100 baroreflex * chemoreflex C pulse oximeter, Hayward, CA), end tidal CO2 (472 1OA capnometer; Hewlett-Packard Co., Andover, MA), central venous pressure, and Introduction sympathetic nerve activity to muscle using microneurography (11). SNA was measured directly by inserting a tungsten microelectrode into Baroreceptor and chemoreceptor reflexes exert considerable in- a nerve fascicle to muscle in the peroneal nerve. Sympathetic bursts fluence on autonomic control of the circulation, especially in were identified by inspection of the mean voltage neurogram and sym- situations involving stressors such as marked changes in blood pathetic activity was calculated as bursts/min X mean burst amplitude pressure and in blood levels of oxygen and carbon dioxide. The and expressed in arbitrary units (12). We also measured minute venti- individual contributions of baroreflexes and their responses to lation using a ventilation monitor (LS-75; Bourns, Riverside, CA). blood pressure alterations and of their Subjects were exposed to gas mixtures intended to induce either chemoreflexes and re- hypoxia (10% 02, 90% N2) or hypercapnia (7% CO2, 93% 02)- Subjects sponses to hypoxia and hypercapnia have been extensively stud- underwent measurement of baseline variables for 3 min while breath- ied in both animals (1, 2) and humans (3, 4). Thus far, however, ing room air. Then using a three-way valve, the subjects were exposed to either the hypoxic (six subjects) or hypercapnic (six subjects) stress- Address reprint requests to Dr. Francois M. Abboud, Department of ors for 5 min. Average values for the 5-min period ofgas exposure were Internal Medicine, University of Iowa College of Medicine, Iowa City, used in the comparisons. In one subject, responses to hypercapnia with IA 52242. and without phenylephrine (PE) were obtained over 3 min because of Received for publication 9 July 1990 and in revised form 14 De- cember 1990. 1. Abbreviations used in this paper: CPT, cold pressor test; CVP, central The Journal of Clinical Investigation, Inc. venous pressure; MBP, mean blood pressure; SNA, sympathetic nerve Volume 87, June 1991, 1953-1957 activity; VE, minute ventilation. Hypoxia, Hypercapnia, and the Baroreflex 1953 inability to comfortably tolerate the stress for a longer period. Note that Conltro Hypoxia Figure 1. Recordings of responses to hypoxia with and without PE were obtained in six subjects sympathetic nerve ac- and to hypercapnia with and without PE in six subjects. Two subjects SNA tivity (SNA) and respi- underwent both protocols (on separate days) and provided data for RESP ratory tracings (RESP) both the hypoxic as well as the hypercapnic stimuli. Exposure to each in a at PE . single subject, of the gas mixtures was performed in the baseline state and during baseline (control; top elevation of systemic pressure using an intravenous infusion of PE. PE PE + Hypoxba left), during hypoxia Infusion of PE was titrated to maintain mean blood pressure (MBP) at SPA (top right), during PE 2 10 mmHg above baseline (thereby activating the baroreflexes). The infusion (bottom left), interventions included: (a) hypoxia or hypercapnia alone; (b) PE alone; and during the combi- (c) hypoxia or hypercapnia during phenylephrine infusion. The order nation of hypoxia and of the interventions was randomly allocated. At least 30 min separated PE infusion. Expiration is indicated by upward movement of the re- the end ofone intervention from the beginning ofthe next. Exposure to spiratory trace and inspiration by downward movement. Note that gas mixtures during the PE infusions was performed only after a con- hypoxia alone increased SNA, whereas PE suppressed SNA. Most stant infusion of PE for at least 10 min to ensure a steady state. importantly, hypoxia during PE resulted in a slight further suppres- During hypoxia, hypocapnia