Baroreceptor Research Articles

Tonic and reflex cardiovascular autonomic control in trained-female rats

The effects of exercise training on cardiovascular and autonomic functions were investigated in female rats. After an aerobic exercise training period (treadmill: 5 days/week for 8 weeks), conscious female Wistar (2 to 3 months) sedentary (S, N = 7) or trained rats (T, N = 7) were cannulated for direct arterial pressure (AP) recording in the non-ovulatory phases. Vagal (VT) and sympathetic tonus (ST) were evaluated by vagal (atropine) and sympathetic (propranolol) blockade. Baroreflex sensitivity was evaluated by the heart rate responses induced by AP changes. Cardiopulmonary reflex was measured by the bradycardic and hypotensive responses to serotonin. Resting bradycardia was observed in T (332 +/- 7 bpm) compared with S animals (357 +/- 10 bpm), whereas AP did not differ between groups. T animals exhibited depressed VT and ST (32 +/- 7 and 15 +/- 4 bpm) compared to S animals (55 +/- 5 and 39 +/- 10 bpm). The baroreflex and cardiopulmonary bradycardic responses were lower in T (-1.01 +/- 0.27 bpm/mmHg and -17 +/- 6 bpm) than in the S group (-1.47 +/- 0.3 bpm/mmHg and -41 +/- 9 bpm). Significant correlations were observed between VT and baroreflex (r = -0.72) and cardiopulmonary (r = -0.76) bradycardic responses. These data show that exercise training in healthy female rats induced resting bradycardia that was probably due to a reduced cardiac ST. Additionally, trained female rats presented attenuated bradycardic responses to baro- and cardiopulmonary receptor stimulation that were associated, at least in part, with exercise training-induced cardiac vagal reduction.

Exercise‐induced neuronal plasticity in central autonomic networks: role in cardiovascular control

It is now well established that brain plasticity is an inherent property not only of the developing but also of the adult brain. Numerous beneficial effects of exercise, including improved memory, cognitive function and neuroprotection, have been shown to involve an important neuroplastic component. However, whether major adaptive cardiovascular adjustments during exercise, needed to ensure proper blood perfusion of peripheral tissues, also require brain neuroplasticity, is presently unknown. This review will critically evaluate current knowledge on proposed mechanisms that are likely to underlie the continuous resetting of baroreflex control of heart rate during/after exercise and following exercise training. Accumulating evidence indicates that not only somatosensory afferents (conveyed by skeletal muscle receptors, baroreceptors and/or cardiopulmonary receptors) but also projections arising from central command neurons (in particular, peptidergic hypothalamic pre-autonomic neurons) converge into the nucleus tractus solitarii (NTS) in the dorsal brainstem, to co-ordinate complex cardiovascular adaptations during dynamic exercise. This review focuses in particular on a reciprocally interconnected network between the NTS and the hypothalamic paraventricular nucleus (PVN), which is proposed to act as a pivotal anatomical and functional substrate underlying integrative feedforward and feedback cardiovascular adjustments during exercise. Recent findings supporting neuroplastic adaptive changes within the NTS-PVN reciprocal network (e.g. remodelling of afferent inputs, structural and functional neuronal plasticity and changes in neurotransmitter content) will be discussed within the context of their role as important underlying cellular mechanisms supporting the tonic activation and improved efficacy of these central pathways in response to circulatory demand at rest and during exercise, both in sedentary and in trained individuals. We hope this review will stimulate more comprehensive studies aimed at understanding cellular and molecular mechanisms within CNS neuronal networks that contribute to exercise-induced neuroplasticity and cardiovascular adjustments.

AFFERENT PATHWAYS INVOLVED IN CARDIOVASCULAR ADJUSTMENTS INDUCED BY HYPERTONIC SALINE RESUSCITATION IN RATS SUBMITTED TO HEMORRHAGIC SHOCK

The peripheral hyperosmolarity elicited by intravenous infusion of hypertonic saline (HS) can be beneficial in treating hemorrhagic shock. However, the neural mechanisms involved in this resuscitation remain unknown. The present study sought to determine the effects of selective baroreceptor denervation on arterial blood pressure response during HS resuscitation in rats submitted to hemorrhagic shock. Male Wistar rats (280-320 g) were anesthetized with thiopental sodium (40 mg/kg, i.v.), and the femoral artery and jugular vein were cannulated for MAP and heart rate recording and HS infusion (3 mol/L NaCl; 0.18 mL/100 g body weight, >2 min). Hemorrhagic shock was obtained by withdrawing blood over 30 min until a MAP of 60 mmHg was obtained. This level of MAP was maintained for a further 30 min through subsequent blood withdrawal or reinfusion. Next, animals were divided into selective aortic and/or carotid denervation or sham groups before infusing HS. Results showed that in the sham group (n = 12), HS infusion increased MAP to levels close to baseline (from 65 +/- 3 to 112 +/- 5 mmHg, 10 min after HS). In the aortic denervated group (n = 10), HS infusion also increased MAP (from 54 +/- 3 to 112 +/- 5 mmHg, 10 min after HS). In contrast, in the carotid denervation group (n = 8), the increase in MAP induced by HS infusion was abolished (from 53 +/- 3 to 73 +/- 12 mmHg, 10 min after HS). These results indicate that in hemorrhaged rats, HS infusion produces a pressor effect that is likely to be mediated through carotid rather than aortic baroreceptors.

Vagal afferent innervation and remodeling in the aortic arch of young-adult fischer 344 rats following chronic intermittent hypoxia

Previously, we have shown that chronic intermittent hypoxia (CIH) impairs baroreflex control of heart rate and augments aortic baroreceptor afferent function. In the present study, we examined whether CIH induces structural changes of aortic afferent axons and terminals. Young-adult Fischer 344 (F344, 4 months old) rats were exposed to room air (RA) or CIH for 35–45 days. After 14–24 days of exposure, they received tracer DiI injection into the left nodose ganglion to anterogradely label vagal afferent nerves. After surgery, animals were returned to their cages to continue RA or CIH exposure. Twenty-one days after DiI injection, the animals were sacrificed and the aortic arch was examined using confocal microscopy. In both RA and CIH rats, we found that DiI-labeled vagal afferent axons entered the wall of the aortic arch, then fanned out and branched into large receptive fields with numerous terminals (flower-sprays, end-nets and free endings). Vagal afferent axons projected much more to the anterior wall than to the posterior wall. In general, the flower-sprays, end-nets and free endings were widely and similarly distributed in the aortic arch of both groups. However, several salient differences between RA and CIH rats were found. Compared to RA control, CIH rats appeared to have larger vagal afferent receptive fields. The CIH rats had many abnormal flower-sprays, end-nets, and free endings which were intermingled and diffused into “bush-like” structures. However, the total number of flower-sprays was comparable ( P>0.05). Since there was a large variance of the size of flower-sprays, we only sampled the 10 largest flower-sprays from each animal. CIH substantially increased the size of large flower-sprays ( P<0.01). Numerous free endings with enlarged varicosities were identified, resembling axonal sprouting structures. Taken together, our data indicate that CIH induces significant remodeling of afferent terminal structures in the aortic arch of F344 rats. We suggest that such an enlargement of vagal afferent terminals may contribute to altered aortic baroreceptor function following CIH.

Aortic baroreceptor function and depressed baroreflex sensitivity following myocardial infarction

Depressed sinoaortic baroreflex control of heart rate following myocardial infarction (MI) is associated with increased morbidity and mortality. The etiology of this autonomic disturbance is unknown but could potentially occur at several levels of the reflex arc. The purpose of this study was to assess whether depressed baroreflex sensitivity (BRS) post-MI is associated with aortic baroreceptor dysfunction.BRS was measured before and 4–8 weeks after anterior MI in 17 chronically-instrumented, trained, conscious dogs. BRS (ms/mm Hg) was defined as the slope of the relationship between changes in systolic blood pressure (SBP) and heart period in response to a bolus dose of phenylephrine (PE). After the effects of MI on BRS were determined, the animals were anesthetized and the aortic depressor nerves (ADN) were isolated from the cervical vagi. Aortic baroreceptor function was measured by direct recording of ADN activity during gradual elevation of SBP induced by PE infusion.BRS was depressed following MI in 7 of these dogs and preserved in the remaining 10. Aortic baroreceptor sensitivity (ABS) defined as the slope of the relationship between changes in ADN activity and SBP was not significantly different between the dogs with depressed BRS compared to the dogs with preserved BRS post-MI.In conclusion, the response of the aortic baroreceptors to an increase in SBP is similar in dogs with and without depressed BRS post-MI. Based on these data, we conclude that depressed reflex control of heart rate following MI is not related to dysfunction of the afferent limb of the sinoaortic baroreflex.

Hydrogen Peroxide Mediates Post‐Excitatory Depression of Baroreceptor Afferent Activity in Vivo

Acute hypertension leads to 'post‐excitatory depression' (PED) of baroreceptor (BR) activity after the period of elevated blood pressure (BP), a phenomenon that contributes to BR resetting. The molecular mechanism of PED is not fully understood. We recently demonstrated that electrical stimulation of isolated BR neurons in vitro generates reactive oxygen species that cause PED of action potential firing after the period of neuronal activation (Hypertension 43(6):1349, 2004). In the present study, we tested the hypothesis that the reactive oxygen species hydrogen peroxide (H2O2) mediates BR PED in vivo. The left aortic depressor nerve (ADN) was draped over a recording/stimulating electrode and crushed centrally to prevent reflex changes in BP in anesthetized C57BL/6 mice. Afferent ADN (BR) activity was recorded before and after a brief period of ADN stimulation (3V, 2ms pulses at 20Hz for 10s). Afferent BR activity was markedly inhibited after the 10s period of electrical stimulation, averaging 50±5% and 80±8% of baseline levels 5 and 60s after the stimulation was terminated (n=7). This PED was abolished after administration of the membrane permeable H2O2 scavenger PEG‐catalase (4000 U, IV) with activity averaging 100±4 and 126±7% of baseline 5 and 60s after ADN stimulation (n=7). PED was unaffected by administration of the saline vehicle in a separate group of mice (n=6). We conclude that H2O2 generated during activation of BR afferents causes PED. This autocrine‐feedback inhibition of BR activity may contribute to rapid BR resetting in acute hypertension. (HL14388, VA)

Chronic Aortic Barodenervation switches salt‐sensitive normotension to salt‐sensitive hypertension in rats

Our prior (EB08 Abs.738.4) cross sectional study suggested that bilateral chronic aortic baroreceptor denervation (AD) induces salt‐sensitive normotension in rats. To assess this in depth, mean arterial pressure (MAP) was measured intra‐arterially over time (3 times) in two groups of conscious Wistar rats. The first time (PreDen) was measured in caudal artery before random sham (SH, n = 7) or real AD (n = 10); the second one was measured in left femoral artery after 7 days on low sodium diet (PostDen LNaD = 0.04% Na) and the third time was measured in right femoral artery after 21 days on high sodium diet (PostDen HNaD = 8% Na). The effectiveness of AD was judged by Box‐Cox transformation of PHE(1) and SNP (2) slope [((( [3 ‐ (HR2‐HR1/ MAP2‐MAP1)] −0.4) ‐1) / ‐0.046)] obtained in conscious state. Salt Sensitivity = SS = (PostDen HNaD MAP ‐ PostDen LNaD MAP, mmHg). Delta of MAP (PostDen MAP ‐ PreDen MAP, mmHg) on both LNaD and HNaD were calculated too. &amp;p = 0.05, *p &lt;0.003 vs SH and + p &lt; 0.01, # p &lt; 0.009 vs LNaD.PreDen PostDen PostDen SS Delta MAP DeltaMAPLNaD HNaD LNaD HNaDSH 105.0 114.0 122.0+ 7.7 9.0 16.7+±2.7 ±1.8 ±1.7 ±2.5 ±2.6 ±2.3AD 101.0 123.2&amp; 134.5*# 11.3 22.2* 33.5*#±2.0 ±2.4 ±2.8 ±2.6 ±2.0 ±2.4ConclusionsWistar rats show salt‐sensitive normotension that chronic AD switches to salt‐sensitive hypertension. Supported by: CONACYT 62282

Involvement of NADPH oxidase‐derived superoxide anion in diabetes‐blunted aortic baroreceptor neuron excitability

NADPH oxidase‐derived superoxide has been identified as key signaling pathway in many pathophysiological processes. Our recent study has indicated that hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channel function is enhanced, which contributes to the blunted aortic baroreceptor (AB) neuron excitability in diabetic state. Therefore, we investigated if NADPH oxidase‐derived superoxide mediates HCN channel activity and cell excitability of AB neurons in streptozotocin (STZ)‐induced diabetic rats. Using western blot and lucigenin chemiluminescence method, we found that protein expression of NADPH oxidase (gp91phox, p22phox, p40phox, p47phox, and p67phox) and superoxide production were higher in nodose ganglia from diabetic rats than that from sham rats. In whole cell patch‐clamp recording, action potential frequency of AB neurons in the diabetic rats was lower than that in the control rats (0.5 ± 0.5 vs. 4.9 ± 0.6 spikes/sec, p&lt;0.05; AB neurons were identified by DiI staining). HCN current density of AB neurons was increased in the diabetic rats, compared with the control rats. In addition, apocynin (30 µM, a NADPH oxidase inhibitor) and tempol (1 mM, a superoxide dismutase mimetic) significantly reduced HCN current density and increased action potential frequency of the AB neurons in diabetic rats. These results indicate that elevation of intracellular NADPH oxidase‐derived superoxide generation contributes to the attenuated AB neuron excitability via enhancing HCN channel activation in diabetic state.

Mechanisms of the ventrolateral medulla on the control of sympathetic activity by central chemoreflex in rats

In the absence of inputs from carotid bodies and cardiopulmonary receptors hypercapnia markedly increases sympathetic nerve discharge (SND) to the heart and blood vessels. In the present study, splanchnic sympathetic nerve discharge (sSND) and phrenic nerve discharge (PND) were recorded in urethane anaesthetized sino‐aortic denervated and vagotomized rats. Hypercapnia (end‐expiratory CO2 from 5% to 10%) increased sSND (δ= 103 ± 7%). Bilateral injection of muscimol (GABA‐A agonist ‐ 2 mM in 30 nl) into the retrotrapezoid nucleus (RTN) eliminated PND and reduced the effect of CO2 on sSND (δ= 56 ± 8%). Injection of AP‐5 (NMDA glutamate receptor antagonist ‐ 100 mM in 50 nl) or DNQX (non NMDA glutamate receptor antagonist ‐ 100 mM in 50 nl) bilaterally into rostroventrolateral medulla (RVLM) reduced PND, but did not change the effect of CO2 on sSND. Bilateral injection of MCPG (metabotropic glutamate receptor antagonist ‐ 100 mM in 50 nL) into the RVLM reduced PND and the effect of CO2 on sSND (δ= 41 ± 7%). In conclusion, RVLM metabotropic receptors and RTN are involved in the increase in sSND produced by CO2.

Characterization of persistent TTX-R Na+ currents in physiological concentration of sodium in rat visceral afferents

Persistent tetrodotoxin-resistant (TTX-R) Na(+) (Na(v)1.9/SCN11A) currents are not normally recorded in vagal afferent neurons (VANs) with 50 mM of extracellular Na(+) although the functional expression of this current was observed in the presence of PGE(2) or forskolin. However, it is uncertain whether this current can be seen under physiological condition (150 mM Na(+)). Using the whole-cell patch-clamp technique, we showed that persistent TTX-R Na(+) currents were expressed in 9 out of 38 VANs bathed in 150 mM Na(+). The current density, but not the whole-cell capacitance, was significantly enhanced in the VANs expressing Nav1.9. Persistent TTX-R Na(+) channels were activated at a more hyperpolarized membrane potential near -60 mV, compared with TTX-sensitive (TTX-S at -40 mV) and TTX-R Na(+) channels (at -20 mV). This indicates that persistent TTX-R Na(+) channels provide a wider activation window than TTX-S and TTX-R Na channels to up-regulate neuronal excitability. These results suggest that the persistent TTX-R Na(+) currents may be involved in the neuronal excitability by setting a lower pressure-discharge threshold and higher discharge frequency of VANs, especially the unique subset and gender-specific distribution of myelinated Ah-type VANs, including Ah-type aortic baroreceptor neurons, identified in our previous study.

Ramp rate of blood pressure changes does not affect aortic afferent sensitivity in anesthetized rats

To investigate whether the rate of change in blood pressure affects the sensitivity of the aortic baroreceptor afferent response, the change in aortic nerve activity (ANA) to two different rates of ramp increase in mean blood pressure (MBP), elicited by phenylephrine administration, was determined in the rat under urethane (1.5gkg−1) anesthesia. The sensitivity of the increase in ANA following a rapid (average ramp rate, 9.14±0.60mmHgs−1, n=11) or gradual (1.78±0.24mmHgs−1, n=11) increase in MBP was 2.03±0.14% and 1.81±0.20% of baseline mmHg−1, respectively. These values were not significantly different from each other (P=0.16). Furthermore, we found no correlation between the rate of ramp increase in MBP and the sensitivity of the increase in ANA (r=0.24, P=0.29, n=22). These results suggest that, at least within the normal physiological range of MBP, the rate of the ramp change in blood pressure does not affect aortic baroreceptor afferent sensitivity in the anesthetized rat.

73: Diabetes Enhances Activation of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels in Aortic Baroreceptor Neurons: Involvement of Angiotensin II

73: Diabetes Enhances Activation of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels in Aortic Baroreceptor Neurons: Involvement of Angiotensin II

Electrophysiological and neuroanatomical evidence of sexual dimorphism in aortic baroreceptor and vagal afferents in rat

Evidence for sexual dimorphism in autonomic control of cardiovascular function is both compelling and confounding. Across healthy and disease populations sex-associated differences in neurocirculatory hemodynamics are far too complex to be entirely related to sex hormones. As an initial step toward identifying additional physiological mechanisms, we investigated whether there is a sex bias in the relative expression of low-threshold-myelinated and high-threshold-unmyelinated aortic baroreceptor afferents in rats. These two types of afferent fibers have markedly different reflexogenic effects upon heart rate and blood pressure and thus the potential impact upon baroreflex dynamics could be substantial. Our results, using a combination of a patch-clamp study of fluorescently identified aortic baroreceptor neurons (ABN) and morphometric analysis of aortic baroreceptor nerve fibers, demonstrate that females exhibit a greater percentage of myelinated baroreceptor fibers (24.8% vs. 18.7% of total baroreceptor fiber population, P < 0.01) and express a functional subtype of myelinated ABN rarely found in age-matched males (11% vs. 2.3%, n = 107, P < 0.01). Interestingly, this neuronal phenotype is more prevalent in the general population of female vagal afferent neurons (17.7% vs. 3.8%, n = 169, P < 0.01), and ovariectomy does not alter its expression but does lessen neuronal excitability. These data suggest there are fundamental neuroanatomical and electrophysiological differences between aortic baroreceptor afferents of female and male rats. Possible explanations are presented as to how such a greater prevalence of low-threshold myelinated afferents could be a contributing factor to the altered baroreflex sensitivity and vagal tone of females compared with males.

GM1 ganglioside contributes to retain the neuronal conduction and neuronal excitability in visceral and baroreceptor afferents

GM1 ganglioside has a great impact on the function of nodes of Ranvier on myelinated fiber, suggesting its potential role to maintain the electrical and neuronal excitability of neurons. Here we first demonstrate that visceral afferent conduction velocity of myelinated and unmyelinated fibers are reduced significantly by tetrodotoxin (TTX) or cholera toxin-B subunits (CTX-B), and only the effects mediated by CTX-B are prevented by GM1 pre-treatment. At soma of myelinated A and unmyelinated C-type nodose ganglion neurons (NGNs), the action potential spike frequency reduced by CTX-B is also prevented by GM1. Additionally, the current density of both TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) Na(+) channels were significantly decreased by CTX-B without changing the voltage-dependent property. These data confirm that endogenous GM1 may play a dominant role in maintaining the electrical and neuronal excitability via modulation of sodium (Na(+)) channel around nodes and soma as well, especially TTX-S Na(+) channel, which is also confirmed by the reduction of spike amplitude and depolarization. Similar data are also extended to fluorescently identified and electrophysiologically characterized aortic baroreceptor neurons. These findings suggest that GM1 plays an important role in the neural modulation of electric and neuronal excitability in visceral afferent system.

Blunted excitability of aortic baroreceptor neurons in diabetic rats: involvement of hyperpolarization-activated channel

Although dysfunction of arterial baroreflex occurs in human and animal models of type-1 diabetes (T1D), the mechanisms involved in the impairment of the baroreflex still remain unclear. The nodose ganglion (NG) contains the cell bodies of the aortic baroreceptor (AB) neurons. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are expressed in AB neurons and play an important role in regulating the cell excitability. We investigated whether the excitability of AB neurons is depressed in streptozotocin (STZ)-induced T1D rats and whether HCN channels are involved in this depression. Using the whole-cell patch clamp technique, we found that AB neuron excitability (action potential frequency at 50 pA current stimulation) in the T1D rats was lower than that in the sham rats (0.4 +/- 0.5 vs. 4.8 +/- 0.6 spikes/s, P < 0.05; AB neurons were identified by DiI staining). In addition, HCN current density in AB neurons from the T1D rats was bigger than that from the sham rats (60.2 +/- 6.1 vs. 30.7 +/- 4.9 pA/pF at test pulse -140 from holding potential -40 mV, P < 0.05). Furthermore, HCN channel blockers (5 mM cesium chloride and 100 microM ZD7288) significantly reduced HCN currents and increased action potential frequency of the AB neurons in sham and T1D rats. Immunofluorescent and western blot analyses demonstrated that the expression of HCN1 and HCN2 channel protein in the NG from the T1D rats was higher than that from the sham rats. These results indicate that the HCN channels influence the excitability of AB neurons, and more importantly, contribute to the decreased excitability of AB neurons in T1D rats.

Effects of Pacing Modes on Cardiac Baroreflex Function in Permanently Paced Patients with Sinus Node Dysfunction

We compared, in patients with sick sinus syndrome, the effects of various pacing modes on baroreceptor (BR)-stroke volume (SV) reflex sensitivity, a method we have closely correlated with BR-heart rate (HR) reflex sensitivity. Impaired autonomic nervous function, such as decreased BR-HR reflex sensitivity, predicts sudden cardiac death. However, in patients with sick sinus syndrome, the effects of various pacing modes on autonomic function are unknown, since chronotropic incompetence precludes its evaluation by measurements of BR-HR reflex sensitivity. We studied 12 recipients of dual-chamber pacemakers with sick sinus syndrome (mean age = 73 +/- 8 years; 8 men). Beat-by-beat blood pressure (BP) and SV were measured during 5-minute runs of AAI, DDD, and VVI pacing, and spectrally analyzed to assess BR-SV reflex sensitivity. Systolic BP was significantly lower (P < 0.01) during VVI (109 +/- 24 mmHg) than during DDD (124 +/- 22 mmHg) or AAI (125 +/- 41 mmHg) pacing. SV was significantly smaller during VVI (36 +/- 23 mL) than during DDD (49 +/- 31 mL) pacing (P < 0.05). BR-SV reflex sensitivity was significantly lower (P < 0.05) during VVI (9.3 +/- 5.7% per mmHg) than during DDD (15.0 +/- 6.5% per mmHg) or AAI (15.5 +/- 6.2% per mmHg) pacing. BR-SV reflex sensitivity was significantly lower during VVI than during AAI or DDD pacing. Atrioventricular synchrony plays an important role in the preservation of BR-SV reflex sensitivity in pacemaker recipients.

Vasopressin in paediatric practice

Arginine vasopressin (AVP) is a nine amino acid peptide hormone, which is synthesized in the hypothalamus as a precursor, transported down the portal system and stored in the posterior pituitary gland. It is also known as argipressin or antidiuretic hormone (ADH) and it is closely related in structure to oxytocin, which is also released from the posterior pituitary. Physiologically, it acts though the kidney with several other hormones to conserve solute-free water, but in hypovolemic states its potent arterial and venoconstrictor properties act to preserve blood pressure. Vasopressin has been used for many years in the treatment of diabetes insipidus and in control of bleeding esophageal varices (utilizing its potent vasoconstrictor effect on the slanchnic circulation), but its role as a pressor agent in the context of resuscitation, septic shock and pediatric cardiac surgery has only emerged in the last few years. Vasopressin is released physiologically in response to a rise in osmolarity, which is sensed within sensitive receptors in the hypothalamus. A fall in osmolarity below 280 mOsmAEkg will trigger its release (1). It acts via V2 receptors to open aquaporin (water channels) in the collecting tubules thereby increasing central water reabsorption. Reduction in afferent transmission from baroreceptors or cardiopulmonary volume receptors associated with hypovolemia or hypotension will also trigger vasopressin release which then acts via V1a receptors of smooth muscle to produce vasoconstriction of both veins and arteries (2). Similarly, increases in circulating ANG11 act via the hypothalamus to trigger release (3). The vasoconstictive effects are specific to different organ beds with the slanchnic bed being particularly sensitive to the circulating concentrations of vasopressin. In addition, increase in vasopressin activity is associated with increased release of corticotrophin releasing hormone via V1b (V3) receptors within the CNS, an increase in release of FV111, Von Willebrand Factor and enhanced platelet aggregation. The physiological effects on the heart are unclear. In the isolated healthy myocyte AVP produces improved contractility (4) probably by increasing intracellular calcium in myocardial cells through a GTP mechanism (5): The integrated position is less clear: pharmacological doses cause coronary vasoconstriction, while improved inotropic performance in pathological states may occur due both primary myocardial effect of secondary effects because of improved coronary perfusion. Pathologically, vasopressin is known to rise in heart failure and conditions of cardiovascular compromise. There are less data in children: in a study of neonates with congenital heart disease, AVP levels in infants with congestive heart and no outflow tract obstruction was significantly higher than normal controls but those with failure and left ventricular outflow tract obstruction had reduced levels (6). The available data suggest that while vasopressin levels are often raised appropriately in hypotensive states because of a variety of conditions this is not necessarily the case. Small studies have been published documenting vasopressin deficiency in catecholamine resistant hypotension (7,8). Vasopressin became of interest when it was observed that organ donors who had brain death and diabetes insipidus were cardiovascularly more stable with reduced inotrope requirements and better organ preservation. Additionally, it was observed that patients who survived cardiac arrest had higher levels of vasopressin compared to nonsurvivors (9). In contrast, there is a correlation of poorer outcome after cardiopulmonary resuscitation with higher levels of endogenous catecholamines (10). These observations led to initial adult studies which questioned whether the purer vasoPediatric Anesthesia 2008 18: 579–581 doi:10.1111/j.1460-9592.2008.02520.x

Dominant role of aortic baroreceptors in the cardiac baroreflex of the rat in situ

The arterial baroreceptors detect changes in blood pressure and form the afferent limb of the baroreflex which acts to buffer changes in pressure through reciprocal regulation of the sympathetic and parasympathetic outflow. We have previously shown that the sympathetic and parasympathetic limbs of the baroreflex operate over different pressure ranges and hypothesised that these differences in regulation of heart rate and sympathetic activity could originate from the baroafferents. We tested this hypothesis using sequential baroafferent denervations in the decerebrate, arterially perfused rat preparation. We found that baroreflex control of heart rate is critically dependent upon the aortic arch afferents with relatively little contribution from the carotid sinuses. Indeed the baroreflex bradycardia was attenuated by 85% ( n = 7) when only one aortic depressor nerve was cut indicating a strongly synergistic interaction between aortic baroafferents. By contrast baroreflex sympathoinhibition was dependent on inputs from all four sites, and the stimulation of any single site could elicit robust sympathoinhibition. These findings were independent of the sequence of baroafferent nerve resection ( n = 15). Perfusion of the isolated carotid sinus ( n = 5) showed that it was possible to elicit baroreflex sympathoinhibition (and changes in vascular resistance) without any significant change in heart rate despite the use of strong stimuli (> 100 mmHg) or repeated pulsatile stimuli. These results indicate fundamental differences in the responses elicited by stimulation of the afferents from the carotid and aortic barosensor sites and suggest that their actions within the nucleus of the solitary tract are functionally specified (sympathetic versus parasympathetic).

Resistant hypertension

Resistant hypertension, defined as a persistent blood pressure over 140/90 mmHg despite the use of three antihypertensive drugs including a diuretic, is unusual. The diagnosis requires ruling out initially pseudoresistance and a lack of compliance with treatment. Ambulatory blood pressure recording allow the recognition of white coat hypertension. When there is a clinical or laboratory suspicion, secondary causes of hypertension should be discarded. Excessive salt intake, the presence of concomitant diseases such as diabetes mellitus, chronic renal disease, obesity, and psychiatric conditions such as panic attacks, anxiety and depression, should also be sought. The presence of target organ damage requires a more aggressive treatment of hypertension. Recent clinical studies indicate that the administration of aldosterone antagonists as a fourth therapeutic line provides significant additional blood pressure reduction, when added to previous antihypertensive regimens in subjects with resistant hypertension. The possible blood pressure lowering effects of prolonged electrical activation of carotid baroreceptors is under investigation.

Is there a preferential loss of aortic baroreceptor C‐fibre activity during the development of atherosclerosis?

Is there a preferential loss of aortic baroreceptor C‐fibre activity during the development of atherosclerosis?