腺苷对家兔颈动脉化学感受器活动的影响

The response of single carotid chemoreceptor afferent fibers upon adenosine acting on the carotid body (CB) was examined in 39 urethan-anesthetized rabbits. Totally 73 units with spontaneous discharge were recorded in our experiment. The results were as follows: (1) Of 55 units, 51 showed an increase in discharge frequency from 0.76 +/- 0.10 to 1.53 +/- 0.23 imp/s. A few new units were recruited concomitantly in response to intracarotid injection of adenosine (10 micrograms/kg). (2) Adding adenosine in the doses of 0.5, 1.5, 10, 50 and 100 micrograms/kg to the perfusate passing through the isolated carotid sinus led to dose-dependent increase in the discharge from 0.51 +/- 0.06 to 0.58 +/- 0.07, 0.78 +/- 0.13, 0.96 +/- 0.15, 1.11 +/- 0.17, 1.34 +/- 0.21 and 1.38 +/- 0.18 imp/s, respectively (P less than 0.001, n = 9 units). (3) In other 9 units with spontaneous discharge rate of 1.30 +/- 0.40 imp/s, the activity was decreased to 0.56 +/- 0.19 imp/s (P less than 0.01) by intracarotid injection of dopamine (50 micrograms/kg). Intracarotid injection of adenosine to the CB pretreated with dopamine still activated the units with an increase in firing rate to 1.07 +/- 0.28 imp/s (P less than 0.01). However, the increment was less prominent as compared with that of adenosine administration before dopamine injection (P less than 0.001). From the results obtained, it is hypothesized that the exciting effect of adenosine on the CB chemoreceptor may be attributed to its action on the presynaptic component of the chemoreceptor complex in attenuating the release of inhibitory transmitter dopamine, and its direct stimulating action on the chemosensory nerve endings.     

Increased carotid body hypoxic sensitivity during acclimatization to hypobaric hypoxia

Mechanisms of ventilatory acclimatization to chronic hypoxia remain unclear. To determine whether the sensitivity of peripheral chemoreceptors to hypoxia increases during acclimatization, we measured ventilatory and carotid sinus nerve responses to isocapnic hypoxia in seven cats exposed to simulated altitude of 15,000 ft (barometric pressure = 440 Torr) for 48 h. A control group (n = 7) was selected for hypoxic ventilatory responses matched to the preacclimatized measurements of the experimental group. Exposure to 48 h of hypobaric hypoxia produced acclimatization manifested as decrease in end-tidal PCO2 (PETCO2) in normoxia (34.5 +/- 0.9 Torr before, 28.9 +/- 1.2 after the exposure) as well as in hypoxia (28.1 +/- 1.9 Torr before, 21.8 +/- 1.9 after). Acclimatization produced an increase in hypoxic ventilatory response, measured as the shape parameter A (24.9 +/- 2.6 before, 35.2 +/- 5.6 after; P less than 0.05), whereas values in controls remained unchanged (25.7 +/- 3.2 and 23.1 +/- 2.7; NS). Hypoxic exposure was associated with an increase in the carotid body response to hypoxia, similarly measured as the shape parameter A (24.2 +/- 4.7 in control, 44.5 +/- 8.2 in acclimatized cats). We also found an increased dependency of ventilation on carotid body function (PETCO2 increased after unilateral section of carotid sinus nerve in acclimatized but not in control animals). These results suggest that acclimatization is associated with increased hypoxic ventilatory response accompanied by enhanced peripheral chemoreceptor responsiveness, which may contribute to the attendant rise in ventilation.     

Interindividual variation in hypoxic ventilatory response: potential role of carotid body

There is considerable interindividual variation in ventilatory response to hypoxia in humans but the mechanism remains unknown. To examine the potential contribution of variable peripheral chemorecptor function to variation in hypoxic ventilatory response (HVR), we compared the peripheral chemoreceptor and ventilatory response to hypoxia in 51 anesthetized cats. We found large interindividual differences in HVR spanning a sevenfold range. In 23 cats studied on two separate days, ventilatory measurements were correlated (r = 0.54, P less than 0.01), suggesting stable interindividual differences. Measurements during wakefulness and in anesthesia in nine cats showed that although anesthesia lowered the absolute HVR it had no influence on the range or the rank of the magnitude of the response of individuals in the group. We observed a positive correlation between ventilatory and carotid sinus nerve (CSN) responses to hypoxia measured during anesthesia in 51 cats (r = 0.63, P less than 0.001). To assess the translation of peripheral chemoreceptor activity into expiratory minute ventilation (VE) we used an index relating the increase of VE to the increase of CSN activity for a given hypoxic stimulus (delta VE/delta CSN). Comparison of this index for cats with lowest (n = 5, HVR A = 7.0 +/- 0.8) and cats with highest (n = 5, HVR A = 53.2 +/- 4.9) ventilatory responses showed similar efficiency of central translation (0.72 +/- 0.06 and 0.70 +/- 0.08, respectively). These results indicate that interindividual variation in HVR is associated with comparable variation in hypoxic sensitivity of carotid bodies. Thus differences in peripheral chemoreceptor sensitivity may contribute to interindividual variability of HVR.     

Effect of chronic hypoxia on cholinergic chemotransmission in rat carotid body.

Current views suggest that oxygen sensing in the carotid body occurs in chemosensory type I cells, which excite synaptically apposed chemoafferent nerve terminals in the carotid sinus nerve (CSN). Prolonged exposure in a low-oxygen environment [i.e., chronic hypoxia (CH)] elicits an elevated stimulus-evoked discharge in chemoreceptor CSN fibers (i.e., increased chemosensitivity). In the present study, we evaluated cholinergic chemotransmission in the rat carotid body in an effort to test the hypothesis that CH enhances ACh-mediated synaptic activity between type I cells and chemoafferent nerve terminals. Animals were exposed in a hypobaric chamber (barometric pressure = 380 Torr) for 9-22 days before evaluation of chemoreceptor activity using an in vitro carotid body/CSN preparation. Nerve activity evoked by ACh was significantly larger (P < 0.01) after CH, suggesting increased expression of cholinergic receptors. Approximately 80% of the CSN impulse activity elicited by ACh (100- or 1,000-microg bolus) in both normal and CH preparations was blocked by the specific nicotinic receptor antagonist mecamylamine (100 microM). CSN activity elicited by acute hypoxia or hypercapnia in normal preparations was likewise blocked (> or =80%) in the presence of 100 muM mecamylamine, but after CH the enhanced CSN activity elicited by acute hypoxia or hypercapnia was not reduced in the presence of 100 or 500 microM mecamylamine. A muscarinic receptor antagonist, atropine (10 microM), and a specific nicotinic receptor alpha7 subunit antagonist, methyllycaconatine (50 nM), blocked approximately 50% of the hypoxia-evoked activity in normal preparations but were ineffective after CH. Prolonged exposure to hypoxia appears to dramatically alter chemotransmission in the carotid body, and may induce alternative neurotransmitter mechanisms and/or electrical coupling between type I cells and chemoafferent nerve terminals.     

Carotid chemoreceptor activity during acute and sustained hypoxia in goats

The role of carotid body chemoreceptors in ventilatory acclimatization to hypoxia, i.e., the progressive, time-dependent increase in ventilation during the first several hours or days of hypoxic exposure, is not well understood. The purpose of this investigation was to characterize the effects of acute and prolonged (up to 4 h) hypoxia on carotid body chemoreceptor discharge frequency in anesthetized goats. The goat was chosen for study because of its well-documented and rapid acclimatization to hypoxia. The response of the goat carotid body to acute progressive isocapnic hypoxia was similar to other species, i.e., a hyperbolic increase in discharge as arterial PO2 (PaO2) decreased. The response of 35 single chemoreceptor fibers to an isocapnic [arterial PCO2 (PaCO2) 38-40 Torr)] decrease in PaO2 of from 100 +/- 1.7 to 40.7 +/- 0.5 (SE) Torr was an increase in mean discharge frequency from 1.7 +/- 0.2 to 5.8 +/- 0.4 impulses. During sustained isocapnic steady-state hypoxia (PaO2 39.8 +/- 0.5 Torr, PaCO2, 38.4 +/- 0.4 Torr) chemoreceptor afferent discharge frequency remained constant for the first hour of hypoxic exposure. Thereafter, single-fiber chemoreceptor afferents exhibited a progressive, time-related increase in discharge (1.3 +/- 0.2 impulses.s-1.h-1, P less than 0.01) during sustained hypoxia of up to 4-h duration. These data suggest that increased carotid chemoreceptor activity contributes to ventilatory acclimatization to hypoxia.     

Role of substance P in hypercapnic excitation of carotid chemoreceptors

Experiments were performed on 17 anesthetized, paralyzed, and artificially ventilated cats to evaluate the importance of substance P-like peptide (SP) on the carotid body responses to CO2. Single or paucifiber carotid chemoreceptor activity was recorded from the peripheral end of the cut carotid sinus nerve. In eight of the cats the influence of SP on hyperoxic hypercapnic responses was studied. While the animals breathed 100% O2, intracarotid infusion of SP (1 microgram.kg-1.min-1, 3 min) increased chemoreceptor activity by +4.8 +/- 0.3 impulses/s. After SP infusion, inhalation of CO2 in O2 caused a rapid increase in activity that reached a peak and then adapted to a lower level, whereas similar levels of CO2 before SP caused only a gradual increase in carotid body discharge rate without any overshoot in response. Furthermore SP significantly increased the magnitude and slope of the CO2 response. In the other nine cats the effect of intracarotid infusion of an SP antagonist, [D-Pro2,D-Trp7,9] SP (10-15 micrograms.kg-1.min-1), on carotid body responses to 1) hyperoxic hypercapnia (7% CO2-93% O2), 2) isocapnic hypoxia (11% O2-89% N2), and 3) hypoxic hypercapnia (11% O2-7% CO2-82% N2) was examined. SP antagonist had no effect on carotid body response to hyperoxic hypercapnia but significantly attenuated the chemoreceptor excitation caused by isocapnic hypoxia and hypoxic hypercapnia. These results suggest that 1) SP may play an important role in carotid body responses to hypoxia but not to CO2, and 2) the mechanisms of stimulation of the carotid body by hypercapnia and by hypoxia differ.     

去甲肾上腺素介导低氧引起家兔颈动脉体神经电活动增加

在30只家兔颈动脉体-窦神经(CSN)标本上, 记录了窦神经中39个对低氧反应敏感的化学感受性单位由去甲肾上腺素(NA)及其拮抗剂引起的反应。结果如下 (1)以低氧的改良台氏液(MTS)灌流标本时, 19个单位放电频率由0.13±0.06增至0.25±0.12 imp/s (P<0.001); (2)在灌流液中加入去甲肾上腺素(10     

Spontaneous action potential generation due to persistent sodium channel currents in simulated carotid body afferent fibers.

The mechanism by which action potentials (APs) are generated in afferent nerve fibers in the carotid body is unknown, but it is generally speculated to be release of an excitatory transmitter and synaptic depolarizing events. However, previous results suggested that Na(+) channels in the afferent nerve fibers play an important role in this process. To better understand the potential mechanism by which Na(+) channels may generate APs, a mathematical model of chemoreceptor nerve fibers that incorporated Hodgkin-Huxley-type Na(+) channels with kinetics of activation and inactivation, as determined previously from recordings of petrosal chemoreceptor neurons, was constructed. While the density of Na(+) channels was kept constant, spontaneous APs arose in nerve terminals as the axonal diameter was reduced to that in rat carotid body. AP excitability and pattern were similar to those observed in chemoreceptor recordings: 1) a random pattern at low- and high-frequency discharge rates, 2) a high sensitivity to reductions in extracellular Na(+) concentration, and 3) a variation in excitability that increased with AP generation rate. Taken together, the results suggest that an endogenous process in chemoreceptor nerve terminals may underlie AP generation, a process independent of synaptic depolarizing events.     

Dependency of hypoxic chemotransduction in cat carotid body on voltage-gated calcium channels.

The hypothesis that the entry of extracellular calcium ions into some compartment, quite possibly the type I cells, through voltage-gated calcium channels (VGCC) is essential for hypoxic chemotransduction in the cat carotid body was tested using an in situ perfusion technique. The neural output of the carotid body of anesthetized, paralyzed, and artificially ventilated cats in response to perfusions with Krebs-Ringer bicarbonate solution (KRB), calcium-free KRB, KRB containing calcium channel blockers, or KRB containing BAY K 8644 was recorded. Selective perfusion of the carotid body with hypoxic calcium-free KRB significantly decreased carotid chemoreceptor activity, suggesting that extracellular calcium is essential for hypoxic chemotransduction. Selective perfusion of the carotid body with hypoxic KRB containing verapamil (10-100 microM), diltiazem (10-100 microM), or nifedipine (10-100 microM) dose dependently attenuated the increase in chemoreceptor activity produced by hypoxia, suggesting that VGCC need to be activated for hypoxic chemotransduction. The carotid body response to hyperoxic KRB containing the calcium channel agonist BAY K 8644 (10 microM) was 267 +/- 87% of hyperoxic control KRB, suggesting that an enhanced influx of calcium ions through VGCC stimulates carotid chemoreceptor activity. Selective perfusion of the carotid body with severely hypoxic KRB containing BAY K 8644 did not increase chemoreceptor activity above that produced by severe hypoxia alone. This suggests that severe hypoxia increases intracellular calcium in some compartment of the carotid body to achieve stimulatory maximum response and that further increase in intracellular calcium does not produce further elevation of neural activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise training improves peripheral chemoreflex function in heart failure rabbits.

An enhancement of peripheral chemoreflex sensitivity contributes to sympathetic hyperactivity in chronic heart failure (CHF) rabbits. The enhanced chemoreflex function in CHF involves augmented carotid body (CB) chemoreceptor activity via upregulation of the angiotensin II (ANG II) type 1 (AT(1))-receptor pathway and downregulation of the neuronal nitric oxide synthase (nNOS)-nitric oxide (NO) pathway in the CB. Here we investigated whether exercise training (EXT) normalizes the enhanced peripheral chemoreflex function in CHF rabbits and possible mechanisms mediating this effect. EXT partially, but not fully, normalized the exaggerated baseline renal sympathetic nerve activity (RSNA) and the response of RSNA to hypoxia in CHF rabbits. EXT also decreased the baseline CB nerve single-fiber discharge (4.9 +/- 0.4 vs. 7.7 +/- 0.4 imp/s at Po(2) = 103 +/- 2.3 Torr) and the response to hypoxia (20.6 +/- 1.1 vs. 36.3 +/- 1.3 imp/s at Po(2) = 41 +/- 2.2 Torr) from CB chemoreceptors in CHF rabbits, which could be reversed by treatment of the CB with ANG II or a nNOS inhibitor. Our results also showed that NO concentration and protein expression of nNOS were increased in the CBs from EXT + CHF rabbits, compared with that in CHF rabbits. On the other hand, elevated ANG II concentration and AT(1)-receptor overexpression of the CBs in CHF state were blunted by EXT. These results indicate that EXT normalizes the CB chemoreflex in CHF by preventing an increase in afferent CB chemoreceptor activity. EXT reverses the alterations in the nNOS-NO and ANG II-AT(1)-receptor pathways in the CB responsible for chemoreceptor sensitization in CHF.     

Role of components of the phagocytic NADPH oxidase in oxygen sensing.

It has been hypothesized that O(2) sensing in type I cells of the carotid body and erythropoietin (EPO)-producing cells of the kidney involves protein components identical to the NADPH oxidase system responsible for the respiratory burst of phagocytes. In the present study, we evaluated O(2) sensing in mice with null mutant genotypes for two components of the phagocytic oxidase. Whole body plethysmography was used to study unanesthetized, unrestrained mice. When exposed to an acute hypoxic stimulus, gp91(phox)-null mutant and wild-type mice increased their minute ventilation by similar amounts. In contrast, p47(phox)-null mutant mice demonstrated increases in minute ventilation in response to hypoxia that exceeded that of their wild-type counterparts: 98.0 +/- 18.0 vs. 20.0 +/- 13.0% (n = 11, P = 0.003). In vitro recordings of carotid sinus nerve (CSN) activity demonstrated that resting (basal) neural activity was marginally elevated in p47(phox)-null mutant mice. With hypoxic challenge, mean CSN discharge was 1.5-fold greater in p47(phox)-null mutant than in wild-type mice: 109.61 +/- 13.29 vs. 72.54 +/- 7.65 impulses/s (n = 8 and 7, respectively, P = 0.026). Consequently, the hypoxia-evoked CSN discharge (stimulus-basal) was approximately 58% larger in p47(phox)-null mutant mice. Quantities of EPO mRNA in kidney were similar in gp91(phox)- and p47(phox)-null mutant mice and their respective wild-type controls exposed to hypobaric hypoxia for 72 h. These findings confirm the previous observation that absence of the gp91(phox) component of the phagocytic NADPH oxidase does not alter the O(2)-sensing mechanism of the carotid body. However, absence of the p47(phox) component significantly potentiates ventilatory and chemoreceptor responses to hypoxia. O(2) sensing in EPO-producing cells of the kidney appears to be independent of the gp91(phox) and p47(phox) components of the phagocytic NADPH oxidase.     

Vesicular glutamate transporter 2-immunoreactive afferent nerve terminals in the carotid body of the rat

The carotid body is a peripheral chemoreceptor that detects decreases in arterial pO₂ and subsequently activates the carotid sinus nerve. The hypoxia-evoked activity of the carotid sinus nerve has been suggested to be modulated by glutamate. In the present study, we investigate the immunohistochemical localization of vesicular glutamate transporters in the carotid body of the rat. Vesicular glutamate transporter 2 (VGLUT2) labeling was closely associated with glomus cells immunoreactive to tyrosine hydroxylase but was not in the cytoplasm of these cells. The VGLUT2 immunoreactivity was observed within nerve endings that were immunoreactive to P2X3 and densely localized inside P2X3-immunoreactive axon terminals. These results suggest that VGLUT2 is localized in the afferent nerve terminals of the carotid body. Glutamate may be released from afferent nerve terminals to modulate the chemosensory activity of the carotid body.     

An important functional role of persistent Na+ current in carotid body hypoxia transduction.

Systemic hypoxia in mammals is sensed and transduced by the carotid body into increased action potential (AP) frequency on the sinus nerve, resulting in increased ventilation. The mechanism of hypoxia transduction is not resolved, but previous work suggested that fast Na(+) channels play an important role in determining the rate and timing of APs (Donnelly, DF, Panisello JM, and Boggs D. J Physiol. 511: 301-311, 1998). We speculated that Na(+) channel activity between APs, termed persistent Na(+) current (I(NaP)), is responsible for AP generation that and riluzole and phenytoin, which inhibit this current, would impair organ function. Using whole cell patch clamp recording of intact petrosal neurons with projections to the carotid body, we demonstrated that I(NaP) is present in chemoreceptor afferent neurons and is inhibited by riluzole. Furthermore, discharge frequencies of single-unit, chemoreceptor activity, in vitro, during normoxia (Po(2) 150 Torr) and during acute hypoxia (Po(2) 90 Torr) were significantly reduced by riluzole concentrations at or above 5 microM, and by phenytoin at 100 microM, without significant affect on nerve conduction time, AP magnitude (inferred from extracellular field), and AP duration. The effect of both drugs appeared solely postsynaptic because hypoxia-induced catecholamine release in the carotid body was not altered by either drug. The respiratory response of unanesthetized, unrestrained 2-wk-old rats to acute hypoxia (12% inspired O(2) fraction), which was measured with whole body plethysmography, was significantly reduced after treatment with riluzole (2 mg/kg ip) and phenytoin (20 mg/kg ip). We conclude that I(NaP) is present in chemoreceptor afferent neurons and serves an important role in peripheral chemoreceptor function and, hence, in the ventilatory response to hypoxia.     

Regulation of chemoreceptor sensitivity in the carotid body: the role of presynaptic sensory nerves

Several neural and vascular mechanisms regulate the sensitivity of carotid body chemoreceptors to hypoxia, hypercapnia, and acidosis. Factors that control blood flow and oxygen delivery in the carotid body along with those that augment or diminish catecholamine release from glomus cells can have major effects on chemoreceptor function. In addition, the sensory nerves themselves may participate in the regulation of chemoreceptor sensitivity. A portion of the carotid body's sensory nerves are presynaptic to glomus cells. In response to stimulation, the sensory nerve terminals exhibit ultrastructural changes that resemble changes associated with increased release of transmitter from motor nerves: 1) the number of small (synaptic) vesicles decreases; and 2) coated vesicles and coated regions of cisternal membrane increase in number during stimulation. If sensory nerves of the carotid body release a neurotransmitters, sensory nerve activity could influence glomus cell secretion of catecholamines or other substances tha modify chemoreceptor sensitivity. Such an effect could be produced in the carotid body by hypoxia and other conditions that stimulate the sensory nerves or it could result from antidromic activity evoked in the sensory nerves by primary afferent depolarization of their terminals in the CNS.     

Differential dynamic baroreflex regulation of cardiac and renal sympathetic nerve activities

Although regional difference in sympathetic efferent nerve activity has been well investigated, whether this regional difference exists in the dynamic baroreflex regulation of sympathetic nerve activity remains uncertain. In anesthetized, vagotomized, and aortic-denervated rabbits, we isolated carotid sinuses and randomly perturbed intracarotid sinus pressure (CSP) while simultaneously recording cardiac (CSNA) and renal sympathetic nerve activities (RSNA). The neural arc transfer function from CSP to CSNA and that from CSP to RSNA revealed high-pass characteristics. The increasing slope of the transfer gain in the frequencies between 0.03 and 0.3 Hz was significantly greater for CSNA than for RSNA (2.96 +/- 0.72 vs. 1.64 +/- 0.73 dB/octave, P < 0.01, n = 9). The difference was hardly explained by the difference in static nonlinear characteristics of CSP-CSNA and CSP-RSNA relationships or by the difference in conduction velocities in the multifiber recording. These results indicate that the central processing in the brain stem differs between CSNA and RSNA. The neural arc of the baroreflex may exert differential effects on the heart and kidney in response to dynamic baroreflex activation.     

Modulation of baroreceptor activity by gene transfer of nitric oxide synthase to carotid sinus adventitia

Administration of nitric oxide (NO) or NO donors to isolated carotid sinus and carotid bodies inhibits the activity of baroreceptor and chemoreceptor afferent nerves. Furthermore, NO synthase (NOS) is present in endothelial cells and in sensory nerves innervating the carotid sinus region. The major goal of this study was to determine whether overexpression of NOS in carotid sinus modulates baroreceptor activity. Rabbits were anesthetized, and adenoviral vectors (5 x 10(8) plaque-forming units) encoding genes for either beta-galactosidase (beta-Gal) or endothelial type III NOS (eNOS) were applied topically to the adventitial surface of one carotid sinus. In some experiments, the NOS inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) was applied to the carotid sinus immediately after the vector. Four to five days later, baroreceptor activity and carotid sinus diameter were measured from the vascularly isolated carotid sinus of the anesthetized rabbits. Transgene expression was confirmed by X-Gal staining of beta-Gal and measurement of NOS activity by citrulline assay. The expression was restricted to the carotid sinus adventitia. Baroreceptor activity was decreased significantly, and the pressure-activity curve was shifted to higher pressures in eNOS-transduced (n = 5) compared with beta-Gal-transduced (n = 5) carotid sinuses. The pressure corresponding to 50% of maximum activity averaged 55 +/- 6 and 76 +/- 7 mmHg in beta-Gal- and eNOS-transduced carotid sinuses, respectively (P < 0.05). Decreased baroreceptor activity was accompanied by a significant increase in carotid diameter in the eNOS-transduced carotid sinuses (n = 5). l-NAME prevented the inhibition of baroreceptor activity and the increase in carotid diameter in eNOS-transduced carotid sinuses (n = 5). We conclude that adenoviral-mediated gene transfer of eNOS to carotid sinus adventitia causes sustained, NO-dependent inhibition of baroreceptor activity and resetting of the baroreceptor function curve to higher pressures.     

Peripheral chemoreceptors in respiratory oscillations

The hypothesis that instability of cardiorespiratory control may depend on the response and sensitivity of carotid body chemoreceptors to arterial blood gases was studied in anesthetized cats under three different experimental conditions. 1) Following administration of the peripheral dopamine receptor blocker [domperidone (0.6-0.8 mg X kg-1, iv)], carotid chemoreceptor activity and its sensitivity to CO2 during hypoxia increased, leading to cardiorespiratory oscillations at low arterial PO2 in four of eight cats. Inhalation of 100% O2 promptly decreased chemoreceptor activity and eliminated the oscillations. Inhalation of CO2 stimulated the chemoreceptor activity and ventilation but did not eliminate the oscillations. Bilateral section of carotid sinus nerves abolished the cardiorespiratory oscillations. The implication is that the dopaminergic system in the carotid body keeps chemoreceptor responses to blood gas stimuli suppressed and hence cardiorespiratory oscillations damped. 2) Hypotension and circulatory delay induced by the partial occlusion of venous return led to cardiorespiratory oscillations at low but not at high arterial PO2. 3) A few cats developed cardiorespiratory oscillations without any particular experimental intervention. These oscillations were independent of arterial PO2 and chemoreceptor activity. Thus it is reasonable to conclude that the peripheral chemoreflex can play a critical role in developing cardiorespiratory oscillations in certain instances.     

Ventilatory control during exercise with peripheral chemoreceptor stimulation: hypoxia vs. domperidone

Hypoxia potentiates the ventilatory response to exercise, eliciting a greater decrease in arterial PCO2 (PaCO2) from rest to exercise than in normoxia. The mechanism of this hypoxia-exercise interaction requires intact carotid chemoreceptors. To determine whether carotid chemoreceptor stimulation alone is sufficient to elicit the mechanism without whole body hypoxia, ventilatory responses to treadmill exercise were compared in goats during hyperoxic control conditions, moderate hypoxia (PaO2 = 38-44 Torr), and peripheral chemoreceptor stimulation with the peripheral dopamine D2-receptor antagonist, domperidone (Dom; 0.5 mg/kg iv). Measurements with Dom were made in both hyperoxia (Dom) and hypoxia (Dom/hypoxia). Finally, ventilatory responses to inspired CO2 at rest were compared in each experimental condition because enhanced CO2 chemoreception might be expected to blunt the PaCO2 decrease during exercise. At rest, PaCO2 decreased from control with Dom (-5.0 +/- 0.9 Torr), hypoxia (-4.1 +/- 0.5 Torr), and Dom/hypoxia (-11.1 +/- 1.2 Torr). The PaCO2 decrease from rest to exercise was not significantly different between control (-1.7 +/- 0.6 Torr) and Dom (-1.4 +/- 0.8 Torr) but was significantly greater in hypoxia (-4.3 +/- 0.7 Torr) and Dom/hypoxia (-3.5 +/- 0.9 Torr). The slope of the ventilation vs. CO2 production relationship in exercise increased with Dom (16%), hypoxia (18%), and Dom/hypoxia (68%). Ventilatory responses to inspired CO2 at rest increased from control to Dom (236%) and Dom/hypoxia (295%) and increased in four of five goats in hypoxia (mean 317%).(ABSTRACT TRUNCATED AT 250 WORDS)     

心房钠泵因子对颈动脉窦压力感受器反射的易化作用

Effects of atriopeptin II (APII) on the carotid sinus baroreflex in anesthetized rats and on the sinus nerve afferent activity in the anesthetized rabbits were investigated. The results were as follows: (1) By perfusing the isolated left carotid sinus with APII (1 microgram/ml) in anesthetized rats (n = 10), the threshold pressure (TP) of the carotid baroreflex did not show any change, while the equilibrium pressure (EP), the saturation pressure (SP) and the operating range (OR) were decreased from 101 +/- 2.8 to 95 +/- 2.0 mmHg (P less than 0.05), 202 +/- 5.2 to 168 +/- 6.1 mmHg (P less than 0.001) and 128 +/- 5.5 to 93 +/- 6.3 mmHg (P less than 0.001), respectively. The function curve of the baroreflex was shifted to the left and downward with a peak slope (PS) increased during perfusing with APII. In contrast, by perfusing the carotid sinus with sodium nitroprusside (NP, 0.5 micrograms/ml), TP and EP remained unchanged, whereas SP and OR were increased from 188 +/- 6.4 to 218 +/- 6.0 mmHg (n = 6, P less than 0.01) and from 107 +/- 6.9 to 132 +/- 7.6 mmHg (P less than 0.05), respectively. The function curve of the baroreflex and its PS were not affected by NP. The sinus nerve afferent activity was quite stable with the perfusion of carotid sinus at constant intrasinus pressure (ISP) in the rabbits (n = 6) and increased during the elevation of ISP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adrenomedullin immunoreactivity in the human carotid body

We studied by immunocytochemistry the expression of AM in human carotid bodies, sampled at autopsy from 16 adult subjects (mean age+/-S.D.: 44.3+/-3.4 years) and from six fetuses (mean gestational age+/-S.D.: 167+/-11 days). No AM immunoreactivity was visible in the type II cells of both series. The percentage of immunoreactive type I cells was higher in the adult subjects (32.3+/-7.7%) with respect to the fetuses (11.8+/-2.7%, P < 0.001). Dark cells showed a higher percentage of positive immunoreaction with respect to light cells, both in adult subjects (61.7+/-13.4% versus 19.2+/-5.2%) and in fetuses (25.3+/-4.4% versus 6.2+/-2.0%). AM may play a role in the regulation of chemoreceptor discharge through paracrine releasing action and/or vasodilator effect. The low expression of AM in fetuses may be ascribed to the absence of pulmonary respiration with lack of regulatory role of the carotid body during the prenatal period.