Arterial Pressure Responses Research Articles

Bilateral superior cervical ganglionectomy attenuates the progression of β-aminopropionitrile-induced aortic dissection in rats

AimsAortic dissection (AD) represents one of the most common aortic emergencies with high incidence of morbidity and mortality. Clinical studies have shown that the increased excitability of the sympathetic nerve may be associated with the formation of AD. In this study, we examined the effects of bilateral superior cervical sympathectomy (SCGx) on the progression of β-aminopropionitrile (BAPN)-induced AD in rats. Main methodsSprague–Dawley rats were randomly divided into three groups, including BAPN, BAPN+SCGx and control groups. For terminal measurements, the mean arterial pressure (MAP) and heart rate (HR) were monitored and the basal sympathetic nerve activity (SNA) was assessed through recording the variation in arterial pressure in response to hexamethonium application. Pathological changes in the aortic wall were observed by histological staining. Matrix metalloproteinase-2 (MMP-2) and MMP-9 concentrations within the aortic wall were analyzed by western blot. Key findingsThe results show that BAPN administration could elevate SNA and cause the formation of AD in rats with a high incidence (67.7%), while SCGx treatment inhibited the elevation of SNA and significantly reduced the incidence (20%). SCGx may suppress the formation of BAPN-induced AD via restraining the rise of HR and reducing the MMP-9 concentration in aortic wall. SignificanceThese results indicate that surgical techniques such as sympathetic nerve block may be a potentially useful therapy for the prevention of AD.

End-Tidal CO2-Guided Chest Compression Delivery Improves Survival in a Neonatal Asphyxial Cardiac Arrest Model.

To determine whether end-tidal CO2-guided chest compression delivery improves survival over standard cardiopulmonary resuscitation after prolonged asphyxial arrest. Preclinical randomized controlled study. University animal research laboratory. 1-2-week-old swine. After undergoing a 20-minute asphyxial arrest, animals received either standard or end-tidal CO2-guided cardiopulmonary resuscitation. In the standard group, chest compression delivery was optimized by video and verbal feedback to maintain the rate, depth, and release within published guidelines. In the end-tidal CO2-guided group, chest compression rate and depth were adjusted to obtain a maximal end-tidal CO2 level without other feedback. Cardiopulmonary resuscitation included 10 minutes of basic life support followed by advanced life support for 10 minutes or until return of spontaneous circulation. Mean end-tidal CO2 at 10 minutes of cardiopulmonary resuscitation was 34 ± 8 torr in the end-tidal CO2 group (n = 14) and 19 ± 9 torr in the standard group (n = 14; p = 0.0001). The return of spontaneous circulation rate was 7 of 14 (50%) in the end-tidal CO2 group and 2 of 14 (14%) in the standard group (p = 0.04). The chest compression rate averaged 143 ± 10/min in the end-tidal CO2 group and 102 ± 2/min in the standard group (p < 0.0001). Neither asphyxia-related hypercarbia nor epinephrine administration confounded the use of end-tidal CO2-guided chest compression delivery. The response of the relaxation arterial pressure and cerebral perfusion pressure to the initial epinephrine administration was greater in the end-tidal CO2 group than in the standard group (p = 0.01 and p = 0.03, respectively). The prevalence of resuscitation-related injuries was similar between groups. End-tidal CO2-guided chest compression delivery is an effective resuscitation method that improves early survival after prolonged asphyxial arrest in this neonatal piglet model. Optimizing end-tidal CO2 levels during cardiopulmonary resuscitation required that chest compression delivery rate exceed current guidelines. The use of physiologic feedback during cardiopulmonary resuscitation has the potential to provide optimized and individualized resuscitative efforts.

Cooperative Oxygen Sensing by the Kidney and Carotid Body in Blood Pressure Control.

Oxygen sensing mechanisms are vital for homeostasis and survival. When oxygen levels are too low (hypoxia), blood flow has to be increased, metabolism reduced, or a combination of both, to counteract tissue damage. These adjustments are regulated by local, humoral, or neural reflex mechanisms. The kidney and the carotid body are both directly sensitive to falls in the partial pressure of oxygen and trigger reflex adjustments and thus act as oxygen sensors. We hypothesize a cooperative oxygen sensing function by both the kidney and carotid body to ensure maintenance of whole body blood flow and tissue oxygen homeostasis. Under pathological conditions of severe or prolonged tissue hypoxia, these sensors may become continuously excessively activated and increase perfusion pressure chronically. Consequently, persistence of their activity could become a driver for the development of hypertension and cardiovascular disease. Hypoxia-mediated renal and carotid body afferent signaling triggers unrestrained activation of the renin angiotensin-aldosterone system (RAAS). Renal and carotid body mediated responses in arterial pressure appear to be synergistic as interruption of either afferent source has a summative effect of reducing blood pressure in renovascular hypertension. We discuss that this cooperative oxygen sensing system can activate/sensitize their own afferent transduction mechanisms via interactions between the RAAS, hypoxia inducible factor and erythropoiesis pathways. This joint mechanism supports our view point that the development of cardiovascular disease involves afferent nerve activation.

Peripheral versus central effect of intravenous moxonidine on rat carotid sinus baroreflex-mediated sympathetic arterial pressure regulation

AimsMoxonidine is a centrally acting antihypertensive agent with a selectivity to I1-imidazoline receptors higher than that to α2-adrenergic receptors. The present study aimed to quantify a peripheral effect of moxonidine on carotid sinus baroreflex-mediated sympathetic arterial pressure (AP) regulation separately from its central effect. Main methodsIn eight anesthetized Wistar rats, changes in efferent sympathetic nerve activity (SNA) and AP in response to a carotid sinus pressure input were compared before and during an intravenous administration of moxonidine (100μgkg−1 bolus followed by a continuous infusion at 200μg·kg−1·h−1). Key findingsMoxonidine significantly narrowed the range of the AP response (55.3±5.8 to 39.1±6.1mmHg, P<0.05) without changing the minimum AP (77.2±6.4 to 80.7±5.1mmHg, not significant). In the neural arc, moxonidine reduced the minimum SNA (56.6±5.9 to 29.7±6.2%, P<0.05) without affecting the range of the SNA response (45.3±5.5 to 40.2±5.0%, not significant). In the peripheral arc, moxonidine increased the intercept (3.0±8.5 to 51.1±7.2mmHg, P<0.01) and reduced the slope (1.28±0.06 to 0.92±0.15mmHg/%, P<0.05). SignificanceMoxonidine increased AP at any given SNA, suggesting that the peripheral vasoconstrictive effect is stronger than generally recognized. The peripheral vasoconstrictive effect of moxonidine may partly offset the vasodilatory effect attained by centrally-mediated sympathoinhibition.

Angiotensin 1-7 administration alters baroreflex sensitivity and renal function in sympathectomized rats

Background: Renin-angiotensin system (RAS) plays an important role in cardiovascular and kidney functions to regulate the systematic blood pressure. The baroreflex sensitivity (BRS) index is a quantitative index that was considered as a prognostic indicator for cardiovascular system risk which is known as heart rate change to blood pressure change ratio ( HR MAP ∆ ∆ ). Sympathetic nerve is an arm of the BRS which may be influenced by RAS vasodilatory arm function. Objectives: To determine the role of angiotensin 1-7 (Ang1-7) accompanied by bilateral renal denervation (RDN) on BRS and renal function. Methods: Male and female anesthetized Wistar rats were subjected to RDN and treated with Ang1-7 (300 and 1000 ng.kg-1.min-1). Mean arterial pressure (MAP) and heart rate (HR) responses to phenylephrine (PE) infusion were measured to determine BRS index. As kidney function markers, the creatinine clearance (CrCl) and urine flow (UF) were also determined. Results: The results showed that BRS increased significantly in RDN male rats treated with Ang1-7 compared to vehicle (P<0.05). BRS attenuates significantly in RDN male rats treated with vehicle or Ang1-7 when compared with non-RDN (control). In female rats, the BRS decreased significantly in Ang1-7 treated group (P<0.05). Also, the BRS was significantly different between non-RDN and RDN female rats treated with Ang1-7 (P<0.05). The ClCr in female and UF in both genders increased by Ang1-7 infusion in RDN and non-RDN rats. The alteration of serum nitrite level by Ang1-7 in non-RDN and RDN groups was gender related. Conclusion: The Ang1-7 infusion could alter the BRS index in RDN rat’s gender dependently. The ClCr response to Ang1-7 infusion in male rats was dose related.

Blood pressure response during normocapnic hyperpnoea is blunted in young women compared to men

We hypothesized that young women have a lower arterial blood pressure (BP) response to high inspiratory and expiratory muscle contractions with normocapnic hyperpnoea compared to age-matched men. To test this hypothesis, the cardiovascular response during voluntary normocapnic incremental hyperpnoea was evaluated in young women and compared to that of young men. An incremental respiratory endurance test (IRET) was performed as follows: target minute ventilation was initially set to 30% of the maximal voluntary ventilation (MVV12) and was increased by 10% MVV12 every 3min. The test was terminated when the subject could not maintain the target%MVV. Heart rate and mean arterial BP (MBP) were continuously recorded. The increase in MBP from the baseline (ΔMBP) during the IRET was lower in women than in men (ΔMBP, men: +32.1±4.6mmHg vs. women: +14.9±3.5mmHg at 8min during IRET). This result suggests that young women exhibit a blunted arterial BP response during high-speed inspiratory and expiratory muscle contractions with normocapnic hyperpnoea compared to young men.

Central chemoreflex activation induces sympatho-excitation without altering static or dynamic baroreflex function in normal rats.

Central chemoreflex activation induces sympatho‐excitation. However, how central chemoreflex interacts with baroreflex function remains unknown. This study aimed to examine the impact of central chemoreflex on the dynamic as well as static baroreflex functions under open‐loop conditions. In 15 anesthetized, vagotomized Sprague‐Dawley rats, we isolated bilateral carotid sinuses and controlled intra‐sinus pressure (CSP). We then recorded sympathetic nerve activity (SNA) at the celiac ganglia, and activated central chemoreflex by a gas mixture containing various concentrations of CO 2. Under the baroreflex open‐loop condition (CSP = 100 mmHg), central chemoreflex activation linearly increased SNA and arterial pressure (AP). To examine the static baroreflex function, we increased CSP stepwise from 60 to 170 mmHg and measured steady‐state SNA responses to CSP (mechanoneural arc), and AP responses to SNA (neuromechanical arc). Central chemoreflex activation by inhaling 3% CO 2 significantly increased SNA irrespective of CSP, indicating resetting of the mechanoneural arc, but did not change the neuromechanical arc. As a result, central chemoreflex activation did not change baroreflex maximum total loop gain significantly (−1.29 ± 0.27 vs. −1.68 ± 0.74, N.S.). To examine the dynamic baroreflex function, we randomly perturbed CSP and estimated transfer functions from 0.01 to 1.0 Hz. The transfer function of the mechanoneural arc approximated a high‐pass filter, while those of the neuromechanical arc and total (CSP‐AP relationship) arcs approximated a low‐pass filter. In conclusion, central chemoreflex activation did not alter the transfer function of the mechanoneural, neuromechanical, or total arcs. Central chemoreflex modifies hemodynamics via sympatho‐excitation without compromising dynamic or static baroreflex AP buffering function.

Evidence for Prohypertensive, Proinflammatory Effect of Interleukin-10 During Chronic High Salt Intake in the Condition of Elevated Angiotensin II Level.

IL-10 (interleukin-10) has been suggested to play a protective role in angiotensin II (AngII)-induced cardiovascular disorders. This study examined the role of endogenous IL-10 in salt-sensitive hypertension and renal injury induced by AngII. Responses to chronic AngII (400 ng/min per kilogram body weight; osmotic minipump) infusion were evaluated in IL-10 gene knockout mice fed with either normal salt diet (0.3% NaCl) or high salt (HS; 4% NaCl) diet, and these responses were compared with those in wild-type mice. Normal salt diets or HS diets were given alone for the first 2 weeks and then with AngII treatment for an additional 2 weeks (n=6 in each group). Arterial pressure was continuously monitored by implanted radio-telemetry, and a 24-hour urine collection was performed by metabolic cages on the last day of the experimental period. Basal mean arterial pressure was lower in IL-10 gene knockout mice than in wild-type (98±3 versus 113±3 mm Hg) mice. Mean arterial pressure responses to normal salt/HS alone or to the AngII+normal salt treatment were similar in both strains. However, the increase in mean arterial pressure induced by the AngII+HS treatment was significantly lower in IL-10 gene knockout mice (15±5% versus 37±3%) compared with wild-type mice. Renal tissue endothelial nitric oxide synthase expression (≈3-folds) and urinary excretion of nitric oxide metabolites, nitrate/nitrite (1.2±0.1 versus 0.2±0.02 µmol/L/24 hours) were higher in IL-10 gene knockout mice compared with wild-type mice. These results indicate that an increase in nitric oxide production helps to mitigate salt-sensitive hypertension induced by AngII and suggest that a compensatory interaction between IL-10 and nitric oxide exists in modulating AngII-induced responses during HS intake.

Plastics and cardiovascular health: phthalates may disrupt heart rate variability and cardiovascular reactivity.

Plastics have revolutionized medical device technology, transformed hematological care, and facilitated modern cardiology procedures. Despite these advances, studies have shown that phthalate chemicals migrate out of plastic products and that these chemicals are bioactive. Recent epidemiological and research studies have suggested that phthalate exposure adversely affects cardiovascular function. Our objective was to assess the safety and biocompatibility of phthalate chemicals and resolve the impact on cardiovascular and autonomic physiology. Adult mice were implanted with radiofrequency transmitters to monitor heart rate variability, blood pressure, and autonomic regulation in response to di-2-ethylhexyl-phthalate (DEHP) exposure. DEHP-treated animals displayed a decrease in heart rate variability (-17% SD of normal beat-to-beat intervals and -36% high-frequency power) and an exaggerated mean arterial pressure response to ganglionic blockade (31.5% via chlorisondamine). In response to a conditioned stressor, DEHP-treated animals displayed enhanced cardiovascular reactivity (-56% SD major axis Poincarè plot) and prolonged blood pressure recovery. Alterations in cardiac gene expression of endothelin-1, angiotensin-converting enzyme, and nitric oxide synthase may partly explain these cardiovascular alterations. This is the first study to show an association between phthalate chemicals that are used in medical devices with alterations in autonomic regulation, heart rate variability, and cardiovascular reactivity. Because changes in autonomic balance often precede clinical manifestations of hypertension, atherosclerosis, and conduction abnormalities, future studies are warranted to assess the downstream impact of plastic chemical exposure on end-organ function in sensitive patient populations. This study also highlights the importance of adopting safer biomaterials, chemicals, and/or surface coatings for use in medical devices.NEW & NOTEWORTHY Phthalates are widely used in the manufacturing of consumer and medical products. In the present study, di-2-ethylhexyl-phthalate exposure was associated with alterations in heart rate variability and cardiovascular reactivity. This highlights the importance of investigating the impact of phthalates on health and identifying suitable alternatives for medical device manufacturing.

Transient endothelial dysfunction induced by sugar-sweetened beverage consumption may be attenuated by a single bout of aerobic exercise

BackgroundThis study assessed whether aerobic exercise would attenuate microvascular endothelial dysfunction induced by commercial sugar-sweetened beverage (SSB) consumption. MethodsEleven healthy males participated in this randomized, single-blind crossover study. Cutaneous microvascular endothelial function was assessed using laser speckle contrast imaging coupled with post-occlusive reactive hyperemia before and after a) consumption of water; b) consumption of a commercial SSB; c) 30min of aerobic exercise followed by water consumption; and d) 30 minutes of aerobic exercise followed by SSB consumption. Blood glucose and arterial pressure responses were also monitored. Volumes of water and SSB consumed (637.39±29.15 mL) were individualized for each participant, ensuring SSB consumption delivered 1 g of sucrose per kg of body weight. Exercise was performed at 75% of the maximal oxygen uptake heart rate. ResultsCompared to water consumption, the commercial SSB elevated blood glucose concentrations in both sedentary (4.69±0.11 vs. 7.47±0.28 mmol/L, P<0.05) and exercised states (4.95±0.13 vs. 7.93±0.15 mmol/L, P<0.05). However, the decrease in microvascular endothelial function observed following sedentary SSB consumption, expressed as the percentage increase from baseline (208.60±22.40 vs. 179.83±15.80%, P=0.01) and the change in peak hyperemic blood flux from basal to post-intervention assessments (−0.04±0.03 vs. −0.12±0.02 ΔCVC, P=0.01), was attenuated following 30min of aerobic exercise. ConclusionsTo our knowledge, this is the first study to provide evidence that a single bout of aerobic exercise may prevent transient SSB-mediated microvascular endothelial dysfunction.

Effects of different input pressure waveforms on the carotid sinus baroreflex-mediated sympathetic arterial pressure response in rats.

Although the pulsatility of an input pressure is an important factor that determines the arterial baroreflex responses, whether the difference in the input waveforms can meaningfully affect the baroreflex function remains unknown. This study aimed to compare baroreflex responses between two distinct pressure waveforms: a forward saw wave (FSW) and a backward saw wave (BSW). In seven anesthetized rats, carotid sinus pressure was exposed to the FSW or the BSW with a mean of 120 mmHg, pulse pressure of 40 mmHg, and pulse frequency of 1 Hz. Changes in efferent sympathetic nerve activity (SNA) and arterial pressure (AP) during six consecutive saw wave trials (FSW1, BSW1, FSW2, BSW2, FSW3, and BSW3) were examined. The steady-state SNA value during FSW1 was 91.1 ± 1.9%, which was unchanged during FSW2 and FSW3 but significantly increased during BSW1 (106.6 ± 3.4%, P < 0.01), BSW2 (110.6 ± 2.5%, P < 0.01), and BSW3 (111.6 ± 2.3%, P < 0.01). The steady-state AP value during FSW1 was 98.2 ± 8.1 mmHg, which was unchanged during FSW2 and FSW3 but significantly increased during BSW1 (106.7 ± 7.4 mmHg, P < 0.01), BSW2 (105.6 ± 7.8 mmHg, P < 0.01), and BSW3 (103.8 ± 7.2 mmHg, P < 0.05). In conclusion, the FSW was more effective than the BSW in reducing mean SNA and AP. The finding could be applied to designing an artificial pulsatile pressure such as that generated by left ventricular assist devices.NEW & NOTEWORTHY This study examined whether the waveforms of an input pressure alone can affect the baroreflex function by using a forward saw wave and a backward saw wave with the same mean pressure, pulse pressure, and pulse frequency. The forward saw wave was more effective than the backward saw wave in reducing sympathetic nerve activity and arterial pressure. The finding could be applied to designing an artificial pulsatile pressure such as that generated by left ventricular assist devices.

Abstract 252: The Capsaicin Sensitive Afferent Neuron Innervating Skeletal Muscle is Abnormal in the Mdx Mouse

Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy caused by a mutation of the dystrophin gene at locus Xp21, located on the short arm of the X chromosome. Muscle wasting and weakness are common in DMD and in the murine mdx model. We previously demonstrated Group III and IV afferent neurons, which innervate skeletal muscle and control blood pressure and heart rate in response to exercise, are abnormal in settings of ischemia and atrophy; such as cardiomyopathy. We hypothesized that these afferent neurons would also display abnormalities in the mdx mouse. To test this hypothesis, we developed a decerebrate mouse model using 10 wk and 6 mo old male BL10 WT and MDX mice to test mean arterial pressure (MAP) responses to intra-arterial capsaicin (IA-Cap; a specific stimulant of group IV afferent neurons). Mice were anesthetized and MAP was continuously recorded with a pressure transducer in the left carotid artery after which the animal was rendered decerebrate. Following decerebration, anesthesia was discontinued and IA-Cap (0,003-1ug/100ul) was delivered via the left common iliac artery. In rats, we have demonstrated this to be a valid model for evaluating MAP responses to activation of metabolically active afferent neurons. We observed that MAP increased in a dose-related fashion in both 10wk and 6 mo old WT and MDX, while 10 wk old MDX mouse had a normal response, the 6 months MDX mouse response was significantly blunted when compared to WT. To test whether these abnormalities are related to the onset of cardiomyopathy, Echocardiography was performed using 6 months old BL10 WT and MDX mice, no abnormality was found in terms of LV dimensions and function in MDX mice comparing with WT mice. Further studies will be performed to determine whether these abnormalities are inherent to changes in the skeletal muscle of the mdx mouse. We conclude that this murine model displays pressor responses to IA-Cap, similar to the rat and that MDX mice have a blunted blood pressure response to IA-Cap. These results indicate that abnormalities exist within the skeletal muscle afferent neurons in the mdx model.

Arterial blood pressure responses to short-term exposure to fine and ultrafine particles from indoor sources – A randomized sham-controlled exposure study of healthy volunteers

ObjectivesParticulate air pollution is linked to adverse cardiovascular effects. The aim of the study was to investigate the effect of short-term exposure to indoor particles on blood pressure (BP). MethodsWe analyzed the association of particle emissions from indoor sources (candle burning, toasting bread, frying sausages) with BP changes in 54 healthy volunteers in a randomized cross-over controlled exposure study. Particle mass concentration (PMC), size-specific particle number concentration (PNC) and lung-deposited particle surface area concentration (PSC) were measured during the 2h exposure. Systolic and diastolic blood pressure were measured before, during, directly, 2, 4 and 24h after exposure. We performed multiple mixed linear regression analyses of different particle metrics and BP. ResultsBP significantly increased with increasing PMC, PSC and PNC resulting from toasting bread. For example, an increase per 10µg/m3 PM10 and PM2.5, systolic BP increased at all time points with largest changes 1h after exposure initiation of 1.5mmHg (95%-CI: 1.1; 1.9) and of 2.2mmHg (95%-CI: 1.3; 3.1), respectively. ConclusionsOur study suggests an association of short-term exposure to fine and ultrafine particles emitted from toasting bread with increases in BP. Particles emitted from frying sausages and candle burning did not consistently affect BP.

Ischemic preconditioning does not alter muscle sympathetic responses to static handgrip and metaboreflex activation in young healthy men.

Ischemic preconditioning (IPC) has been hypothesized to elicit ergogenic effects by reducing feedback from metabolically sensitive group III/IV muscle afferents during exercise. If so, reflex efferent neural outflow should be attenuated. We investigated the effects of IPC on muscle sympathetic nerve activity (MSNA) during static handgrip (SHG) and used post‐exercise circulatory occlusion (PECO) to isolate for the muscle metaboreflex. Thirty‐seven healthy men (age: 24 ± 5 years [mean ± SD]) were randomized to receive sham (n = 16) or IPC (n = 21) interventions. Blood pressure, heart rate, and MSNA (microneurography; sham n = 11 and IPC n = 18) were collected at rest and during 2 min of SHG (30% maximal voluntary contraction) and 3 min of PECO before (PRE) and after (POST) sham or IPC treatment (3 × 5 min 20 mmHg or 200 mmHg unilateral upper arm cuff inflation). Resting mean arterial pressure was higher following sham (79 ± 7 vs. 83 ± 6 mmHg, P < 0.01) but not IPC (81 ± 6 vs. 82 ± 6 mmHg, P > 0.05), while resting MSNA burst frequency was unchanged (P > 0.05) with sham (18 ± 7 vs. 19 ± 9 bursts/min) or IPC (17 ± 7 vs. 19 ± 7 bursts/min). Mean arterial pressure, heart rate, stroke volume, cardiac output, and total vascular conductance responses during SHG and PECO were comparable PRE and POST following sham and IPC (All P > 0.05). Similarly, MSNA burst frequency, burst incidence, and total MSNA responses during SHG and PECO were comparable PRE and POST with sham and IPC (All P > 0.05). These findings demonstrate that IPC does not reduce hemodynamic responses or central sympathetic outflow directed toward the skeletal muscle during activation of the muscle metaboreflex using static exercise or subsequent PECO.

Interaction of GABA and norepinephrine in the lateral division of the bed nucleus of the stria terminals in anesthetized rat, correlating single-unit and cardiovascular responses

The bed nucleus of the stria terminalis (BST) consists of multiple anatomically distinct nuclei. The lateral division, which receives dense noradrenergic innervation, has been implicated in cardiovascular regulation and modulation of responses to stress. This study is performed to identify the cardiovascular and single-unit responses of the lateral BST to norepinephrine (NE), involved adrenoceptors, and possible interaction with GABAergic system of the BST in urethane-anesthetized rats. NE, adrenoreceptor antagonists, and GABAA antagonist were microinjected into the lateral division of BST, while arterial pressure (AP), heart rate (HR), and single-unit responses were simultaneously recorded.NE microinjected into the lateral division of BST produced depressor and bradycardic responses. The decrease in AP and HR to NE was blocked by prazosin, an α1-adrenoreceptor antagonist, but not by yohimbine, an α2 antagonist.Furthermore, injections of the GABAA receptor antagonist, bicuculline methiodide (BMI), into the lateral BST abolished the NE-induced depressor and bradycardic responses. We also observed single-unit responses consisting of excitatory and inhibitory responses correlated with cardiovascular function to the microinjection of NE. In conclusion, these data provide the first evidence that microinjection of NE in the lateral division of BST produces depressor and bradycardic responses in urethane-anesthetized rat. The depressor and bradycardiac response are mediated by local α1- but not α2-adrenoceptors. α1-AR activates the GABAergic system within the BST, which in turn produces depressor and bradycardic responses.

Changes in acute pulmonary vascular responsiveness to hypoxia during a progressive ascent to high altitude (5300m).

What is the central question of this study? Do the pulmonary vascular responses to hypoxia change during progressive exposure to high altitude and can alterations in these responses be related to changes in concentrations of circulating biomarkers that affect the pulmonary circulation? What is the main finding and its importance? In our field study with healthy volunteers, we demonstrate changes in pulmonary artery pressure suggestive of remodelling in the pulmonary circulation, but find no changes in the acute responsiveness of the pulmonary circulation to changes in oxygenation during 2 weeks of exposure to progressive hypoxia. Pulmonary artery pressure changes were associated with changes in erythropoietin, 8-isoprostane, nitrite and guanosine 3',5'-cyclic monophosphate. We sought to determine whether changes in pulmonary artery pressure responses to hypoxia suggestive of vascular remodelling occur during progressive exposure to high altitude and whether such alterations are related to changes in concentrations of circulating biomarkers with known or suspected actions on the pulmonary vasculature during ascent. We measured tricuspid valve transvalvular pressure gradients (TVPG) in healthy volunteers breathing air at sea level (London, UK) and in hypoxic conditions simulating the inspired O2 partial pressures at two locations in Nepal, Namche Bazaar (NB, elevation 3500m) and Everest Base Camp (EBC, elevation 5300m). During a subsequent 13day trek, TVPG was measured at NB and EBC while volunteers breathed air and hyperoxic or hypoxic mixtures simulating the inspired O2 partial pressures at the other locations. For each location, we determined the slope of the relationship between TVPG and arterial oxygen saturation (SaO2) to estimate the pulmonary vascular response to hypoxia. Mean TVPG breathing air was higher at any SaO2 at EBC than at sea level or NB, but there was no change in the slope of the relationship between SaO2 and TVPG between locations. Nitric oxide availability remained unchanged despite increases in oxidative stress (elevated 8-isoprostane). Erythropoietin, pro-atrial natriuretic peptide and interleukin-18 levels progressively increased on ascent. Associations with TVPG were observed only with erythropoietin, 8-isoprostane, nitrite and guanosine 3',5'-cyclic monophosphate. Although the increased TVPG for any given SaO2 at EBC suggests that pulmonary vascular remodelling might occur during 2weeks of progressive hypoxia, the lack of change in the slope of the relationship between TVPG and SaO2 indicates that the acute pulmonary vascular responsiveness to changes in oxygenation does not vary within this time frame.

Sub-chronic lead exposure produces β1-adrenoceptor downregulation decreasing arterial pressure reactivity in rats

Lead is considered a causative factor for hypertension and other cardiovascular diseases. AimsTo investigate the effects of sub-chronic lead exposure on blood pressure reactivity and cardiac β1-adrenoceptor activity and to evaluate whether the effects found in vitro are similar to those found in vivo. Main methodsMale Wistar rats were randomly distributed into two groups: control rats (Ct) and rats administered drinking water containing 100ppm lead (Pb) for 30days. Key findingsBlood pressure in the Pb rats increased starting from the first week of treatment until the end of the study [systolic blood pressure, Ct: 122±4 vs. Pb: 143±3mmHg; diastolic blood pressure, Ct: 63±4 vs. Pb: 84±4mmHg]. The heart rate was also increased (Ct: 299±11 vs. Pb: 365±11bpm), but the pressure reactivity to phenylephrine was decreased. Losartan and hexamethonium exhibited a greater reduction in blood pressure of Pb rats than in the Ct rats. Isoproterenol increased the left ventricular systolic and end-diastolic pressure, and heart rate only in Ct rats, suggesting that lead induced β1-adrenoceptor downregulation. Indomethacin reduced the blood pressure and heart rate in the Pb rats, suggesting the involvement of cyclooxygenase-derived products (which are associated with reduced nitric oxide bioavailability) in this process. SignificanceThese findings offer further evidence that the effects of sub-chronic lead exposure in vitro can be reproduced in vivo—even at low concentrations—thus triggering mechanisms for the development of hypertension. Therefore, lead should be considered an environmental risk factor for cardiovascular disease.

Lack of Association Between Adrenoreceptor Genotype and the Vasoconstriction Response to Dexmedetomidine.

An exaggerated vasoconstriction response to dexmedetomidine, an α-2 adrenergic agonist, has been associated with 2 genotypes: a deletion in the α-2B adrenoreceptor gene ( ADRA2B deletion) and SNP rs9922316 in the gene for protein kinase C type β ( PRKCB). We hypothesized that children with a marked systemic vascular resistance index (SVRI) increase following intravenous dexmedetomidine bolus would carry these genotypes. Following institutional review board approval, DNA samples from 16 children with transplanted hearts who participated in a study in the cardiac catheterization laboratory of hemodynamic responses to dexmedetomidine boluses underwent genotyping by polymerase chain reaction (PCR) amplification and PCR Sanger sequencing for the ADRA2B deletion and for PRKCB rs9922316. A wide range of SVRI (-12% to +76%, median 33%) and mean arterial blood pressure (MAP; -7% to +50%, median 26%) responses to dexmedetomidine was observed. The responses were not significantly different among genotype groups. An association between exaggerated SVRI or MAP responses and either ADRA2B deletion or PRKCB rs9922316 was not observed.

Erectile Dysfunction in Wistar Audiogenic Rats Is Associated With Increased Cavernosal Contraction and Decreased Neuronal Nitric Oxide Synthase Protein Expression

To test the hypothesis that naive Wistar audiogenic rats (WARs) display erectile dysfunction (ED), which is associated with increased sympathetic-mediated contractile tone and decreased nitric oxide-mediated relaxation responses of the cavernous tissue. Changes in the ratio of the maximal intracavernosal pressure-mean arterial pressure after the electrical stimulation of the right major pelvic ganglion were determined in vivo. Cavernosal contractility was induced by electrical field stimulation and phenylephrine. In addition, nonadrenergic-noncholinergic (NANC)-induced relaxation was determined. Rho-kinase (ROCK) pathway proteins, neuronal nitric oxide synthase (nNOS) protein expression, and endothelial nitric oxide synthase (eNOS) and extracellular signal-regulated kinase 1/2 activities were determined by Western blot. WARs display a significant decrease in maximal intracavernosal pressure-mean arterial pressure responses suggesting ED in this strain. Sympathetic-mediated contractile responses were increased in WARs and contractile responses to phenylephrine were not changed. The increased sympathetic-mediated contractile responses were not associated with changes in the ROCK pathway. On the other hand, NANC-mediated relaxation responses were significantly reduced in WARs. This functional response was accompanied by decreased nNOS and total eNOS protein expressions, augmented phosphorylated eNOS, and decreased extracellular signal-regulated kinase 1/2 phosphorylation levels. Our data have demonstrated that naive WARs display ED in vivo that is associated with increased sympathetic-mediated contractile responses and decreased NANC-mediated relaxation responses. The increase in contractile responses is independent of the ROCK pathway, and the changes in relaxation responses are associated with a decrease in nNOS protein expression, which may activate compensatory mechanisms in the cavernous tissue.

The predictive value of dynamic arterial elastance in arterial pressure response after norepinephrine dosage reduction in patients with septic shock

Objective: To assess whether dynamic arterial elastance(Ea(dyn))can be used to predict the reduction of arterial pressure after decreasing norepinephrine (NE) dosage in patients with septic shock. Methods: A prospective observational cohort study was conducted. Thirty-two patients with septic shock and mechanical ventilationwere enrolledfrom January 2014 to December 2015 in ICU of Wuxi People's Hospital of Nanjing Medical University. Hemodynamic parameters were recorded by pulse contour cardiac output(PiCCO)monitoring technology before and after decreasing norepinephrine dosage. Ea(dyn) was defined as the ratio of pulse pressure variation (PPV) to stroke volume variation (SVV). Mean arterial pressure(MAP) variation was calculated after decreasing the dose of NE. Response was defined as a ≥15% decrease of MAP. AUC was plotted to assess the value of Ea(dyn) in predicting MAP response. Results: A total of 32 patients were enrolled in our study, with 13 responding to NE dose decrease where as the other 19 did not. Ea(dyn) was lower in responders than in nonresponders (0.77±0.13 vs 1.09±0.31, P<0.05). Baseline Ea(dyn) was positively correlated with systolic blood pressure variation, diastolic blood pressure variation, systemic vascular resistance variation and MAP variation(r=0.621, P=0.000; r=0.735, P=0.000; r=0.756, P=0.000; r=0.568, P=0.000 respectively). However, stoke volume variation, baseline level of systemic vascular resistance and NE baseline dose were not correlated with Ea(dyn) baseline value(r=0.264, P=0.076; r=0.078, P=0.545; r=0.002, P=0.987 respectively). Ea(dyn)≤0.97 predicted a decrease of MAP when decreasing NE dose, with an area under the receiver-operating characteristic curve of 0.85.The sensitivity was 100.0% and specificity was 73.7%. Conclusions: In septic shock patients treated with NE, Ea(dyn) is an index to predict the decrease of arterial pressure in response to NE dose reduction.