Fall In Arterial Blood Pressure Research Articles

HIGH SALT DIET ALTERS CEREBROVASCULAR RESISTANCE IN RESPONSE TO ORTHOSTATIC TEST IN HEALTHY YOUNG INDIVIDUALS

Objective: High salt (HS) diet has been shown to impairs vascular reactivity in animal models, by increasing vasoconstriction to different stimuli. Response to orthostasis occurs via activation of baroreceptor reflex leading to increase in total peripheral resistance that prevents significant fall of arterial blood pressure (ABP) while standing up, aiming to preserve cerebral perfusion pressure. We recently showed that HS diet physiologically suppresses sympathetic arm of autonomic control in healthy humans (Stupin et al. Nutrients 2021; 13:1731. https://doi.org/10.3390/nu13051731). Present study aimed to assess the effect of HS diet on cerebral vasoreactivity in response to orthostatic load. Design and method: Twenty-seven young healthy participants (F:21, M:6, age range 19–24) consumed 7-day low-salt (LS) diet (<2.3 g NaCl /day) and afterwards 7-day HS diet (>11.2 g NaCl/day). In response to orthostatic test cerebral and systemic hemodynamic parameters, arterial blood pressure, heart rate variability and heart rate, and were recorded simultaneously with transcranial Doppler ultrasound and The Task Force® Monitor. Results: Subjects maintained normotension during HS diet. Diastolic blood pressure, as well as mean cerebral blood flow (CBF) and the velocity time integral decreased, while cerebral pulsatility index increased after standing up following both dietary protocols. However, while no change was observed in total peripheral resistance, cerebrovascular resistance significantly increased in response to orthostasis only after HS diet. Baroreflex sensitivity (BRS), sympathetic neural control, serum plasma renin activity and aldosterone, and urine noradrenaline and vanillylmandelic acid concentration was significantly decreased in HS diet. Conclusions: Results demonstrated that following 7-day HS diet, enhanced cerebral autoregulation preserves CBF and is manifested as increased cerebral vascular resistance, in conditions with blunted BRS and sympathetic activity. The study has been published in Eur J Appl Physiol. 2023 Jan 4. doi: 10.1007/s00421-022-05124-w. Online ahead of print.

Nischarin Is Not the Functional I1 Imidazoline Receptor Involved in Blood Pressure Regulation.

Imidazoline receptor antisera selected/Nischarin was proposed several years ago as the functional entity for the I1 medullary receptors (I1Rs) targeted, together with α2-adrenoceptors, by the centrally acting antihypertensive drugs, such as clonidine. The objective of this study was to test this assumption using a pyrroline analog of clonidine, LNP599, which, unlike clonidine and related compounds, displays high selectivity toward I1Rs. Cardiovascular effects of LNP599 (3 mg/kg intravenous) were evaluated in anesthetized, artificially ventilated nischarin mutant rats expressing a truncated form of nischarin lacking the putative imidazoline binding site. LNP599 induced a rapid and pronounced fall in arterial blood pressure in wild-type animals (-42.7% ± 11.0% after 15 minutes), associated with a ≈30% heart rate reduction. Similar effects were obtained in homozygous and heterozygous nischarin mutant rats. The observation that the hypotensive response to I1R activation is not affected by the absence of the putative imidazoline binding site on nischarin strongly suggests that nischarin cannot be regarded as the functional I1R. Carbohydrate regulation was improved in nischarin mutant rats, further supporting the conclusion that nischarin and I1R are 2 distinct molecular entities.

Activation of the 5-HT7 receptor but not nitric oxide synthase is necessary for chronic 5-hydroxytryptamine-induced hypotension.

What is the central question of this study? What mechanisms account for the hypotension observed during chronic elevations in circulating 5-hydroxytryptamine in rats? What is the main finding and its importance? Chronic 5-hydroxytryptamine-induced hypotension requires continued activation of the 5-HT7 receptor subtype but does not require NO, an outcome that resolves previous conflicting results. Therapeutic interruption of the hypotensive actions of 5-HT under pathophysiological conditions can only be achieved through blockade of the 5-HT7 receptor. Low dose infusion of 5-hydroxytryptamine (5-HT) to rats causes both an acute and a chronic fall in arterial blood pressure. The 5-HT7 receptor subtype plays a critical part in the observed hypotension. Acute (minutes to hours) 5-HT infusion shows no depressor role for nitric oxide (NO), but 5-HT depressor responses under chronic conditions suggest that NO production may be critical. We test the hypothesis that NO contributes to the chronic, but not the acute, depressor response to 5-HT. We compared the role of NO and 5-HT7 receptors in 5-HT-induced hypotension under acute and chronic conditions in the same animal. Mean arterial pressure and heart rate were measured by radiotelemetry in conscious rats during 5days of saline or 5-HT (25μgkg-1 min-1 ; osmotic pump) infusion and for 2days after infusion was stopped. To quantify the contributions of NO and the 5-HT7 receptor to 5-HT-induced hypotension, the nitric oxide synthase (NOS) inhibitor l-NAME or the selective 5-HT7 receptor antagonist SB-267790 were given at 1, 3 and 5days of chronic infusion, and 1 day after 5-HT infusion pumps were removed. Nω -Nitro-l-arginine methyl ester (l-NAME) caused a pressor response of the same magnitude in the absence or presence of 5-HT infusion. Conversely, SB-269970 did not affect mean arterial pressure in the absence of 5-HT infusion and reversed the 5-HT-induced depressor response at each time point. Our findings demonstrate that acute and chronic 5-HT-induced hypotension does not require NOS activation but does require continued activation of the 5-HT7 receptor.

Consumption of Anacardium Occidentale L. (Cashew Nuts) Inhibits Oxidative Stress through Modulation of the Nrf2/HO-1 and NF-kB Pathways.

Ischemia/reperfusion injury is a severe disorder associated with a high mortality. Several antioxidant and pharmacological properties of cashew nuts (Anacardium occidentale L.) and its metabolites from different countries have recently been described. It is a medicinal plant with important therapeutic effects. This study aimed to verify the effect of an oral administration of cashew nuts in a rat model of ischemia/reperfusion (I/R). Adult male rats were subjected to intestinal I/R injury by clamping the superior mesenteric artery for 30 min and then allowing animals to 1 h of reperfusion. Rats subjected to I/R of the gut showed a significant increase in different biochemical markers. In particular, we evaluated lipid peroxidation, tissue myeloperoxidase activity, protein carbonyl content, reactive oxygen species generation and decreased antioxidant enzyme activities. Western blot analysis showed the activation of the NRF2 and NF-kB pathways. Increased immunoreactivity to nitrotyrosine, PARP, P-selectin, and ICAM-1 was observed in the ileum of rats subjected to I/R. Administration of cashew nuts (100 mg/kg) significantly reduced the mortality rate, the fall in arterial blood pressure, and oxidative stress and restored the antioxidant enzyme activities by a mechanism involving both NRF2 and NF-kB pathways. Cashew nuts treatments reduced cytokines plasma levels, nitrotyrosine, and PARP expression as well as adhesion molecules expressions. Additionally, cashew nuts decreased the intestinal barrier dysfunction and mucosal damage, the translocation of toxins and bacteria, which leads to systemic inflammation and associated organs injuries in particular of liver and kidney. Our study demonstrates that cashew nuts administration exerts antioxidant and pharmacological protective effects in superior mesenteric artery occlusion–reperfusion shock.

Ventilatory responses of the clown knifefish, Chitala ornata, to hypercarbia and hypercapnia.

The aim of the present study was to determine the roles of externally versus internally oriented CO2/H+-sensitive chemoreceptors in promoting cardiorespiratory responses to environmental hypercarbia in the facultative air-breathing fish, Chitala ornata (the clown knifefish). Fish were exposed to environmental acidosis (pH ~ 6.0) or hypercarbia (≈ 30torr PCO2) that produced changes in water pH equal to the pH levels of the acidotic water to distinguish the relative roles of CO2 versus H+. We also injected acetazolamide to elevate arterial levels of PCO2 and [H+] in fish in normocarbic water to distinguish between internal and external stimuli. We measured changes in gill ventilation frequency, air breathing frequency, heart rate and arterial blood pressure in response to each treatment as well as the changes produced in arterial PCO2 and pH. Exposure to normocarbic water of pH 6.0 for 1h did not produce significant changes in any measured variable. Exposure to hypercarbic water dramatically increased air breathing frequency, but had no effect on gill ventilation. Hypercarbia also produced a modest bradycardia and fall in arterial blood pressure. Injection of acetazolamide produced similar effects. Both hypercarbia and acetazolamide led to increases in arterial PCO2 and falls in arterial pH although the changes in arterial PCO2/pH were more modest following acetazolamide injection as were the increases in air breathing frequency. The acetazolamide results suggest that the stimulation of air breathing was due, at least in part, to stimulation of internally oriented CO2/H+ chemoreceptors monitoring blood gas changes.

The link between narcolepsy and autonomic cardiovascular dysfunction: a translational perspective

Narcolepsy is a rare disease that entails excessive daytime sleepiness, often associated with sudden episodes of muscle weakness known as cataplexy. Narcolepsy with cataplexy (NC) is due to the loss of hypothalamic neurons that release the neuropeptides orexin A and B. Orexin neuron projections prominently target brain structures involved in wake-sleep state switching and the central autonomic network. This review provides an updated summary of the links between NC and autonomic cardiovascular dysfunction from a translational perspective. The available evidence suggests that, compared with control subjects, the heart rate in patients and animal models with NC is variable during wakefulness and normal to high during sleep. Responses of the heart rate to internal stimuli (arousal from sleep, leg movements during sleep, defense response) are blunted. These alterations result from orexin deficiency and, at least during wakefulness before sleep, involve decreased parasympathetic modulation of the heart rate. On the other hand, NC in patients and animal models is associated with a blunted fall in arterial blood pressure from wakefulness to sleep, and particularly to the REM state, coupled to a variable decrease in arterial blood pressure during wakefulness. The former effect is caused, at least in part, by deranged control of the heart, whereas the latter may be due to decreased vasoconstrictor sympathetic activity. Systematic studies are warranted to help clarify whether and how the links between NC and autonomic dysfunction impact on the cardiovascular risk of patients with narcolepsy.

Cardiorespiratory action of opioid/tachykinin agonist peptide hybrid in anaesthetized rats: Transduction pathways

AWL3106 composed of opioid (dermorphin) and tachykinin (substance P7–11) pharmacophores is a new compound with high analgesic potency and markedly reduced ability to induce tolerance and dependence.The present study aimed to determine the respiratory and cardiovascular responses evoked by this peptide in urethane-chloralose anaesthetized, spontaneously breathing rats in the presence or absence of vagal connection.Intravenous injection of AWL3106 at a dose of 0.3μmol/kg in intact rats resulted in apnoea lasting 5.1 ± 0.7s. Breathing that followed was of diminished frequency (F) and augmented tidal volume (VT) with no significant impact on minute ventilation. AWL3106-challenge induced biphasic fall in arterial blood pressure with no effect on heart rate. Midcervical and supranodosal sectioning the vagal nerves prevented the occurrence of the apnoea and abrogated the post-AWL3106 reduction in F but failed to eliminate the increase in VT. Hypotensive response appeared to be less profound following supranodose vagotomy. NaloxoneHCl abolished solely the occurrence of apnoea. However additional blockade of tachykinin NK1 receptors with SR140333 was required to abolish VT increase, deceleration of breathing and to markedly suppress AWL3106-induced hypotension.The present study shows that extravagally controlled stimulation of VT maintains fairly regular ventilation by levelling the bradypnoeic effects. Although the peptide showed no cardiac effects, hypotension occurring beyond the vagal loop may limit future therapeutic benefits of this chimeric compound.

Ostreolysin A/Pleurotolysin B and Equinatoxins: Structure, Function and Pathophysiological Effects of These Pore-Forming Proteins.

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

Abstract PR461

Background & Objectives: Pancuronium was marketed in 1964. Use of pancuronium is limited in patients with impaired liver and renal function. Atracurium was introduced in 1982. Atracurium besylate slowly loses potency with time at the rate of approximately 6% per year under refrigeration. Rate of loss in potency increases to approximately 5% per month at 25°C. This study was designed to compare the effect of atracurium versus pancuronium on endotracheal intubation after administration of intubating doses on intubating conditions and cardiovascular parameters in Myanmar population. Materials & Methods: Randomized, prospective, comparative, clinical study of sixty patients (30 for Atracurium & 30 for Pancuronium), age between 20-50 years with ASA I and II who underwent elective surgery requiring GA/ IPPV. After induction with propofol 2.5mg kg-1, 30 patients in group A were given atracurium 0.5mg kg-1 intravenously and 30 patients in group B were received pancuronium 0.1mg kg -1. The first intubation attempt was made 3 minutes after administration of the neuromuscular blocking agent. The heart rate and SpO2 changes were recorded every minute from just before injection of neuromuscular blocking agent till 12 minutes. The changes in arterial blood pressure were also recorded every 3 minutes till 12 minutes after injection of NMBA. Intubation conditions were assessed as excellent, good, fair and poor based on jaw relaxation, position of vocal cords, response of the diaphragm to intubation and the grading at the view of laryngoscopy. The times taken for intubation were also recorded. Results: There were no statistically significant differences in pre-operative haemodynamic data. Atracurium provided more jaw relaxations (p=0.026), better laryngoscopic view (p = 0.028), better vocal cord paralysis & better diaphragmatic relaxation (p = 0.038) and better intubating grading (p = 0.028) than pancuronium. Total time taken for intubation was more prolong with pancuronium (p < 0.01). It was concluded that atracurium provided better intubating conditions than pancuronium. Atracurium caused a slight fall in arterial blood pressure from the baseline but it was not statistically significant. Atracurium had lacked hypertensive response to intubation and provided better haemodynamic stability than pancuronium. Pancuronium caused rapid increase and decrease in blood pressure and had hypertensive stress response to intubation at 6 minutes, which was statistically significant (p < 0.05). Pancuronium caused significant increase in heart rate than atracurium, which was statistically significant at every minute. Conclusion: Atracurium provided that better intubating condition and haemodynamic stability than pancuronium. Presented at ANZCA 2016 as ePoster.

Blood pressure lowering, vasodilator and cardiac-modulatory potential of Carum roxburghianum seed extract

In current study, we describe blood pressure (BP)-lowering, endothelium-dependent, and independent vasodilator and cardio-modulatory actions of Carum roxburghianum seed. The crude extract of C. roxburghianum seed (Cr.Cr) induced dose-dependent (10–100 mg/kg) fall in arterial BP of anaesthetized rats. In isolated rabbit aorta, Cr.Cr (0.3–10 mg/mL) inhibited high K+ (80 mM) and phenylephrine (PE, 1 µM)-induced contractions, like verapamil and papaverine. In endothelium-intact rat aortic preparations, Nω-nitro-l-arginine methyl ester hydrochloride-sensitive vasodilator activity was observed with Cr.Cr, which also relaxed endothelium-denuded aorta tissues. In guinea-pig atria, Cr.Cr initially caused mild cardiac stimulation, followed by inhibition, as shown by papaverine. These results reveal that cardiovascular effects of C. roxburghianum seed extract are mediated possibly through combination of Ca++ antagonist, nitric oxide modulating and phosphodiesterase inhibitory mechanisms, though further in-depth studies are required for elucidating precise mode of action.

Effect of Deep Brain Stimulation on Sympathetic outflow in humans (LB733)

Electric deep brain stimulation (DBS) in midbrain nuclei in humans alters cardiovascularparameters, presumably by modulating autonomic and baroreflex function. Baroreflex modulation of sympathetic outflow is crucial for cardiovascular regulation and is hypothesized to occur at two distinct brain locations. This study aimed to evaluate sympathetic outflow in humans with DBS electrodes during ON and OFF stimulation of specific midbrain nuclei known to regulate cardiovascular function.Muscle sympathetic nerve activity (MSNA) was recorded during DBS ON and OFF in patients with chronic neuropathic pain (n=7) and Parkinson’s disease (n=10). Arterial blood pressure (ABP), heart rate and respiration were monitored during the recording session and spontaneous vasomotor and cardiac baroreflex sensitivity (BRS) were assessed. Head‐up tilt testing was performed separately in the Parkinson’s patients post‐operatively.Stimulation of the dorsal most part of the subthalamic nucleus (STN) and ventrolateral periaqueductal gray (PAG) resulted in improved vasomotor BRS, decreased MSNA burst frequency and ABP, unchanged burst amplitude distribution and a reduced fall in ABP after tilt. Stimulation of the dorsolateral PAG resulted in a shift in burst amplitude distribution towards larger amplitudes, decreased spontaneous BP variability and unchanged burst frequency, BRS and ABP.Baroreflex regulation of sympathetic outflow occurs in the STN and PAG. Our results may have implications in understanding abnormal sympathetic discharge in cardiovascular disease and provide an opportunity for therapeutic targeting.Grant Funding Source: supported by, BHF, NIHR BRC

Powikłania u chorych leczonych metodą plazmaferezy na oddziale intensywnej terapii

Plasmapheresis is one of the methods of extracorporeal blood purification involving the removal of inflammatory mediators and antibodies. The procedure is used in a variety of conditions, including autoimmune diseases. The aim of the present study was to analyse the incidence of plasmapheresis-related complications in patients treated in the intensive care unit (ICU). The analysis involved 370 plasmapheresis procedures in 54 patients. The data were collected from patients' medical records, including procedure protocols. The most common diseases treated with plasmapheresis included: myasthenia gravis (33.3%), Guillain-Barre syndrome (14%), Lyell's syndrome (9.3%), systemic lupus erythematosus (7.4%), and thrombotic thromcytopenic purpura (7.4%). The adverse side effects observed most frequently during plasma filtration were: fall in arterial blood pressure (8.4% of all procedures), arrhythmias (3.5%), sensations of cold with temporarily elevated temperature and paresthesias (1.1%, each). In most cases the symptoms were mild and transient. Severe and life-threatening episodes, i.e. shock, fall in arterial blood pressure requiring pressor amines, persistent arrhythmias and haemolysis, developed in 2.16% of procedures. Plasmapheresis can be considered a relatively safe method of treatment of ICU patients. Continuous observation and proper monitoring of patients provided by highly trained medical personnel are essential for its safety.

English

The leaf of&nbsp;Acalypha torta&nbsp;Muell. (Euphorbiaceae) is used as folk remedy in Nigeria for the treatment of hypertension. Effects of extracts of&nbsp;A. torta&nbsp;leaf on the blood pressure of anaesthetized cats were studied to examine this claim. The ethanol extract produced a significant (p &lt; 0.0001) and dose - dependent fall in arterial blood pressure. The extract inhibited adrenaline - induced contraction of isolated rabbit aortic strips and produced a significant (p &lt; 0.0001) and dose - dependent increase in the rate of flow of physiologic fluid through the rat hind-quarters preparation. Both evidences indicate relaxant effect of the ethanol extract on vascular smooth muscle. Calcium chloride - induced tachycardia was abolished following administration of the extract. It had no effect on the rate of contraction of the isolated rabbit heart, but reduced the force of contraction. Column chromatography was performed and Fraction L, eluted with distilled water, was found to be responsible for the reduction in blood pressure. &nbsp; Key words:&nbsp;Acalypha torta,&nbsp;hypertension, antihypertensive, cat.

Postexercise hypotension and sustained postexercise vasodilatation: what happens after we exercise?

A single bout of aerobic exercise produces a postexercise hypotension associated with a sustained postexercise vasodilatation of the previously exercised muscle. Work over the last few years has determined key pathways for the obligatory components of postexercise hypotension and sustained postexercise vasodilatation and points the way to possible benefits that may result from these robust responses. During the exercise recovery period, the combination of centrally mediated decreases in sympathetic nerve activity with a reduced signal transduction from sympathetic nerve activation into vasoconstriction, as well as local vasodilator mechanisms, contributes to the fall in arterial blood pressure seen after exercise. Important findings from recent studies include the recognition that skeletal muscle afferents may play a primary role in postexercise resetting of the baroreflex via discrete receptor changes within the nucleus tractus solitarii and that sustained postexercise vasodilatation of the previously active skeletal muscle is primarily the result of histamine H(1) and H(2) receptor activation. Future research directions include further exploration of the potential benefits of these changes in the longer term adaptations associated with exercise training, as well as investigation of how the recovery from exercise may provide windows of opportunity for targeted interventions in patients with hypertension and diabetes.

Baroreceptor-mediated activation of sympathetic nerve activity to salivary glands

Salivary gland function is regulated by both the sympathetic and parasympathetic nervous systems. Previously we showed that the basal sympathetic outflow to the salivary glands (SNASG) was higher in hypertensive compared to normotensive rats and that diabetes reduced SNASG discharge at both strains. In the present study we sought to investigate how SNASG might be modulated by acute changes in the arterial pressure and whether baroreceptors play a functional role upon this modulation. To this end, we measured blood pressure and SNASG discharge in Wistar–Kyoto rats (WKY-intact) and in WKY submitted to sinoaortic denervation (WKY-SAD). We made the following three major observations: (i) in WKY-intact rats, baroreceptor loading in response to intravenous infusion of the phenylephrine evoked an increase in SNASG spike frequency (81%, p<0.01) accompanying the increase mean arterial pressure (ΔMAP: +77±14mmHg); (ii) baroreceptor unloading with sodium nitroprusside infusion elicited a decrease in SNASG spike frequency (17%, p<0.01) in parallel with the fall in arterial blood pressure (ΔMAP: −30±3mmHg) in WKY-intact rats; iii) in the WKY-SAD rats, phenylephrine-evoked rises in the arterial pressure (ΔMAP: +56±6mmHg) failed to produce significant changes in the SNASG spike frequency. Taken together, these data show that SNASG increases in parallel with pharmacological-induced pressor response in a baroreceptor dependent way in anaesthetised rats. Considering the key role of SNASG in salivary secretion, this mechanism, which differs from the classic cardiac baroreflex feedback loop, strongly suggests that baroreceptor signalling plays a decisive role in the regulation of salivary gland function.

Peripheral vascular response to inspiratory breath hold in paediatric homozygous sickle cell disease

New Findings• What is the central question of this study?Autonomic nervous dysfunction is implicated in complications of sickle cell anaemia (SCA). In healthy adults, a deep inspiratory breath hold (IBH) elicits rapid transient SNS- mediated vasoconstriction detectable using Laser Doppler Flux (LDF) assessment of the finger-tip cutaneous micovasculature.• What is the main finding and its importance?We demonstrate significantly increased resting peripheral blood flow and sympathetic activity in African children with SCA compared to sibling controls and increased sympathetic stimulation in response to vasoprovocation with DIG.This study is the first to observe an inverse association between resting peripheral blood flow and haemoglobin oxygen saturation (SpO2). These phenomena may be an adaptive response to the hypoxic exposure in SCA.There is increasing evidence that autonomic dysfunction in adults with homozygous sickle cell (haemoglobin SS) disease is associated with enhanced autonomic nervous system-mediated control of microvascular perfusion. However, it is unclear whether such differences are detectable in children with SS disease. We studied 65 children with SS disease [38 boys; median age 7.2 (interquartile range 5.1–10.6) years] and 20 control children without symptoms of SS disease [8 boys; 8.7 (5.5–10.8) years] and recorded mean arterial blood pressure (ABP) and daytime haemoglobin oxygen saturation (). Cutaneous blood flux at rest (RBF) and during the sympathetically activated vasoconstrictor response to inspiratory breath hold (IBH) were measured in the finger pulp of the non-dominant hand using laser Doppler fluximetry. Local factors mediating flow motion were assessed by power spectral density analysis of the oscillatory components of the laser Doppler signal. The RBF measured across the two study groups was negatively associated with age (r=−0.25, P < 0.0001), ABP (r=−0.27, P= 0.02) and daytime (r=−0.30, P= 0.005). Children with SS disease had a higher RBF (P= 0.005) and enhanced vasoconstrictor response to IBH (P= 0.002) compared with control children. In children with SS disease, higher RBF was associated with an increase in the sympathetic interval (r=−0.28, P= 0.022). The SS disease status, daytime and age explained 22% of the variance in vasoconstrictor response to IBH (P < 0.0001). Our findings suggest that blood flow and blood flow responses in the skin of young African children with SS disease differ from those of healthy control children, with increased resting peripheral blood flow and increased sympathetic stimulation from a young age in SS disease. They further suggest that the laser Doppler flowmetry technique with inspiratory breath hold manoeuvre appears to be robust for use in young children with SS disease, to explore interactions between , ABP and autonomic function with clinical complications, e.g. skin ulceration.

Hypotensive effect of Gentiana floribunda is mediated through Ca++ antagonism pathway

BackgroundGentiana floribunda was investigated for the possible hypotensive and vasodilator activities in an attempt to rationalize its traditional use in hypertension.MethodsThe crude extract of Gentiana floribunda (Gf.Cr) was studied in anaesthetized rats and isolated thoracic aorta tissues.ResultsGf.Cr which tested positive for presence of flavonoids, saponins, sterols, tannins and terpenes caused dose-dependent (3.0-100 mg/kg) fall in arterial blood pressure (BP) of rats under anaesthesia. In rat aortic ring preparations denuded of endothelium, Gf.Cr at concentration range of 1.0-10 mg/mL relaxed high K+ (80 mM) and phenylephrine (PE, 1 μM)-induced contractions and shifted Ca++ dose–response curves to right, similar to that caused by verapamil. It also suppressed PE (1 μM) control peak responses at 0.3-1.0 mg/mL, obtained in Ca++-free medium, as exhibited by verapamil. Pre-treatment of tissues with Gf.Cr produced rightward non-parallel shift of PE-curves with decline of maximum contractile response. The vasodilator effect of Gf.Cr was endothelial-independent, as it was not blocked by Nω-nitro-L-arginine methyl ester hydrochloride, atropine and indomethacin in endothelium-intact aortic tissues.ConclusionsThese data indicate that BP-lowering action of Gentiana floribunda occurred via Ca++ antagonism (inhibition of Ca++ ingress and release from intracellular stores), which provides pharmacological basis to justify its effectiveness in hypertension.

Hemodynamic changes in lipid emulsion therapy (SMOFlipid) for bupivacaine toxicity in swines

To evaluate the hemodynamic changes following SMOFlipid emulsion therapy with after bupivacaine intoxication in swines. Large White pigs were anesthetized with thiopental, tracheal intubation was performed and mechanical ventilation was instituted. Hemodynamic variables were recorded with invasive pressure monitoring and pulmonary artery catheterization (Swan-Ganz catheter). After a 30-minute resting period, 5 mg.kg(-1) of bupivacaine by intravenous injection was administered and new hemodynamic measures were performed 1 minute later; the animals were than randomly divided into two groups and received 4 ml.kg(-1) of saline solution or 4 ml.kg(-1) of SMOFlipid emulsion 20%. Hemodynamic changes were then re-evaluated at 5, 10, 15, 20 and 30 minutes. Bupivacaine intoxication caused fall in arterial blood pressure, cardiac index, ventricular systolic work index mainly and no important changes in vascular resistances. SMOFlipid emulsion therapy was able to improve blood pressure mainly by increasing vascular resistance since the cardiac index had no significant improvement in our study. Hemodynamic results of the use of lipid emulsion in bupivacaine intoxication were better than the control group. The SMOFlipid emulsion is a option for reversing hypotension in cases of intoxication by bupivacaine.

Blood pressure lowering effect of Tylophora hirsuta wall

Crude hydromethanolic extract of Tylophora hirsuta (Th.Cr) was studied in spontaneous hypertensive Wistar rats for possible effects on high blood pressure and heart rate. In the absence of atropine, fall in arterial blood pressure was 64±7 mmHg at the dose of 100 mg/kg while in the presence of atropine, there was no effect on arterial blood pressure suggesting cholinergic receptor blockade. Fall in heart rate, in the absence of atropine, was 218±8 beats per minute (BPM) while, fall in heart rate, in the presence of atropine was 110±5.6 BPM, indicating that the action is through cholinergic muscarinic receptors as atropine is a typical anticholinergic drug. The percent fall in blood pressure and heart rate were standardized versus acetylcholine; standard cholinergic drug. Th.Cr tested mildly positive for alkaloids, flavonoids and strongly positive for terpenes and terpenoids, and saponins. α- Amyrin acetate was isolated from the n-hexane fraction of Th.Cr for the first time from T. hirsuta. The results confirm the presence of acetylcholine like substances in T. hirsuta that provide a basis for its traditional use in treatment of hypertension. The action may be attributed to the phytochemicals like flavonoids, saponins, terpenes and terpenoids and α- amyrin acetate isolated for the first time from the plant.

Control of sympathetic vasomotor tone by catecholaminergic C1 neurones of the rostral ventrolateral medulla oblongata

AimsIncreased sympathetic tone in obstructive sleep apnoea results from recurrent episodes of systemic hypoxia and hypercapnia and might be an important contributor to the development of cardiovascular disease. In this study, we re-evaluated the role of a specific population of sympathoexcitatory catecholaminergic C1 neurones of the rostral ventrolateral medulla oblongata in the control of sympathetic vasomotor tone, arterial blood pressure, and hypercapnia-evoked sympathetic and cardiovascular responses.Methods and resultsIn anaesthetized rats in vivo and perfused rat working heart brainstem preparations in situ, C1 neurones were acutely silenced by application of the insect peptide allatostatin following cell-specific targeting with a lentiviral vector to express the inhibitory Drosophila allatostatin receptor. In anaesthetized rats with denervated peripheral chemoreceptors, acute inhibition of 50% of the C1 neuronal population resulted in ∼50% reduction in renal sympathetic nerve activity and a profound fall in arterial blood pressure (by ∼25 mmHg). However, under these conditions systemic hypercapnia still evoked vigorous sympathetic activation and the slopes of the CO2-evoked sympathoexcitatory and cardiovascular responses were not affected by inhibition of C1 neurones. Inhibition of C1 neurones in situ resulted in a reversible fall in perfusion pressure and the amplitude of respiratory-related bursts of thoracic sympathetic nerve activity.ConclusionThese data confirm a fundamental physiological role of medullary catecholaminergic C1 neurones in maintaining resting sympathetic vasomotor tone and arterial blood pressure. However, C1 neurones do not appear to mediate sympathoexcitation evoked by central actions of CO2.