Adrenergic Receptor Sensitivity Research Articles

Sex differences in sympathetic transduction in black and white adults: implications for racial disparities in hypertension and cardiovascular disease risk.

The prevalence of hypertension in non-Hispanic black (BL) individuals is the greatest of any racial/ethnic group. Whereas women generally display lower rates of hypertension than men of the same background, BL women display a similar if not greater burden of hypertension compared with BL men. The risk for cardiovascular disease and related events is also highest in BL individuals. Given the importance of the sympathetic nervous system for the regulation of the cardiovascular system, a growing body of literature has investigated sympathetic function in BL and non-Hispanic white (WH) individuals. Here, we are focused on emerging evidence indicating that sympathetic function may be altered in BL individuals, with particular emphasis on the process by which bursts of muscle sympathetic nerve activity (MSNA) are transduced into vasoconstriction and increases in blood pressure (sympathetic vascular transduction). To synthesize this growing body of literature we discuss sex and race differences in 1) sympathetic outflow, 2) sympathetic vascular transduction, and 3) adrenergic receptor sensitivity. Sex differences are discussed foremost, to set the stage for new data indicating a sex dimorphism in sympathetic regulation in BL individuals. Specifically, we highlight evidence for a potential neurogenic phenotype including greater adiposity-independent sympathetic outflow and enhanced sympathetic vascular transduction in BL men that is not observed in BL women. The implications of these findings for the greater hypertension and cardiovascular disease risk in BL adults are discussed along with areas that require further investigation.

Sex-Related Differences in Self-Reported Symptoms at Diagnosis in Pheochromocytomas and Paragangliomas.

Biological sex can play a role in the severity of certain diseases. Our objective was to evaluate whether sex-related differences affect the signs and symptoms of pheochromocytomas and paragangliomas (PPGLs) at presentation. We reviewed the records of patients with PPGLs at our center from 1995 to 2022. Our study included 385 patients with PPGLs: 118 (30.6%) head and neck paragangliomas (HNPGLs), 58 (15.1%) thoracoabdominal paragangliomas (TAPGLs) and 209 (54.3%) pheochromocytomas (PHEOs). The cohort consisted of 234 (60.8%) women and 151 (39.2%) men. At diagnosis, more women than men presented with headaches (47.5% vs 32.4%; P = .007); however, more men presented with diabetes (21.1% vs 12.5%; P = .039). When subdivided by tumor location, headaches occurred more often in women with HNPGLs and TAPGLs (31.0% vs 11.4%; P = .0499 and 60.0% vs 21.7%; P = .0167). More men presented with diabetes among patients with PHEOs (28.2% vs 11.2%; P = .0038). In regard to nonsecretory PPGLs, women presented with a higher prevalence of headaches (46.9% vs 3.6%; P = .0002), diaphoresis (16.3% vs 0.0%; P = .0454), and palpitations (22.4% vs 0.0%; P = .0057). In patients with secretory tumors, women presented with more headaches (58.9% vs 42.7%; P = .0282) and men with more diabetes (29.3% vs 12.5%; P = .0035). In our cohort, more women presented with headaches across all tumor types and secretory statuses. More men presented with diabetes among patients with PHEOs and secretory tumors. In nonsecretory PPGLs, women had more adrenergic symptoms. These findings can be explained by differences in adrenergic receptor sensitivity, self-reported symptoms, and possibly other vasoactive peptides and sex-hormone status.

Renal Transplantation in Pure Autonomic Failure.

Renal Transplantation in Pure Autonomic Failure.

The effect of Adrenaline on the contractility of the Right Ventricular Myocardium in rat pups with altered Serotonin concentration in Ontogenesis

Serotonin is a monoamine neurotransmitter and hormone that exerts its various actions by binding to the receptor membrane in cells. 5-HT2B receptors are actively involved in embryonic morphogenesis and regulate the development of the heart. 5-HT4 and 5-HT2B are involved in myocardial contractility and affect the temporal parameters of regulation. One of the main mechanisms controlling cardiac activity is also connected with the effect of catecholamines on adrenergic receptors of cardiomyocytes, which mediate the action of the sympathetic nervous system, being the main factor contributing to multiple changes in the development of myocardial cell function. In the given study, there is reliable data provided to indicate that the effect of different concentrations of adrenaline leads to a decrease in contractility of the right ventricular myocardium in 7-day-old and 14-day-old rat pups with an altered serotonin concentration, which was created by a blockade of the synthesis of serotonin and the membrane serotonin transporter in the embryonic period of ontogenesis. The total duration of myocardial contraction is decreased in experimental groups of animals. Thus, the smallest decrease in the time of contraction and relaxation in comparison with other groups is observed in 7-day-old rat pups with an excess of serotonin; in 14-day-old rat pups with a lack of serotonin. Thus, a change in the concentration of serotonin in prenatal ontogenesis can possibly affect the sensitivity of adrenergic receptors in postnatal ontogenesis.

The Vasoactive Effect of Perivascular Adipose Tissue and Hydrogen Sulfide in Thoracic Aortas of Normotensive and Spontaneously Hypertensive Rats.

The objective of this study was to investigate the vasoregulatory role of perivascular adipose tissue (PVAT) and its mutual interaction with endogenous and exogenous H2S in the thoracic aorta (TA) of adult normotensive Wistar rats and spontaneously hypertensive rats (SHRs). In SHRs, hypertension was associated with cardiac hypertrophy and increased contractility. Regardless of the strain, PVAT revealed an anticontractile effect; however, PVAT worsened endothelial-dependent vasorelaxation. Since H2S produced by both the vascular wall and PVAT had a pro-contractile effect in SHRs, H2S decreased the sensitivity of adrenergic receptors to noradrenaline in Wistar rats. While H2S had no contribution to endothelium-dependent relaxation in Wistar rats, in SHRs, H2S produced by the vascular wall had a pro-relaxant effect. We observed a larger vasorelaxation induced by exogenous H2S donor in SHRs than in Wistar rats. Additionally, in the presence of PVAT, this effect was potentiated. We demonstrated that PVAT of the TA aggravated endothelial function in SHRs. However, H2S produced by the TA vascular wall had a pro-relaxation effect, and PVAT revealed anti-contractile activity mediated by the release of an unknown factor and potentiated the vasorelaxation induced by exogenous H2S. All these actions could represent a form of compensatory mechanism to balance impaired vascular tone regulation.

Fructose Intake Impairs the Synergistic Vasomotor Manifestation of Nitric Oxide and Hydrogen Sulfide in Rat Aorta.

In this study, we evaluated the effect of eight weeks of administration of 10% fructose solution to adult Wistar Kyoto (WKY) rats on systolic blood pressure (SBP), plasma and biometric parameters, vasoactive properties of the thoracic aorta (TA), NO synthase (NOS) activity, and the expression of enzymes producing NO and H2S. Eight weeks of fructose administration did not affect SBP, glycaemia, or the plasma levels of total cholesterol or low-density and high-density lipoprotein; however, it significantly increased the plasma levels of γ-glutamyl transferase and alanine transaminase. Chronic fructose intake deteriorated endothelium-dependent vasorelaxation (EDVR) and increased the sensitivity of adrenergic receptors to noradrenaline. Acute NOS inhibition evoked a reduction in EDVR that was similar between groups; however, it increased adrenergic contraction more in fructose-fed rats. CSE inhibition decreased EDVR in WKY but not in fructose-fed rats. The application of a H2S scavenger evoked a reduction in the EDVR in WKY rats and normalized the sensitivity of adrenergic receptors in rats treated with fructose. Fructose intake did not change NOS activity but reduced the expression of eNOS and CBS in the TA and CSE and CBS in the left ventricle. Based on our results, we could assume that the impaired vascular function induced by increased fructose intake was probably not directly associated with a decreased production of NO, but rather with impairment of the NO–H2S interaction and its manifestation in vasoactive responses.

Ketamine: yay or neigh? Implications for cardiovascular regulation and considerations for field use.

Ketamine: yay or neigh? Implications for cardiovascular regulation and considerations for field use.

Paroxetine Attenuates Cardiac Hypertrophy Via Blocking GRK2 and ADRB1 Interaction in Hypertension.

BackgroundADRB1 (adrenergic receptor beta 1) responds to neuroendocrine stimulations, which have great implications in hypertension. GRK2 (G protein‐coupled receptor kinase 2) is an essential regulator for many G protein‐coupled receptors and subsequent cell signaling cascades, but its role as a regulator of ADRB1 and associated cardiac hypertrophy in hypertension remains to be elucidated.Methods and ResultsIn this study, we found the expressions of GRK2 and ADRB1 in peripheral blood mononuclear cells were positively associated with blood pressure levels in hypertensive patients and with their expression in heart. In vitro evidence showed a direct interaction in ADRB1 and GRK2 and genetic depletion of GRK2 blocks epinephrine‐induced upregulation of hypertrophic and fibrotic genes in cardiomyocytes. Meanwhile, we discovered a selective serotonin reuptake inhibitor paroxetine specifically blockades GRK2 and ADRB1 interaction. In vivo, paroxetine treatment ameliorates hypertension‐induced cardiac hypertrophy, dysfunction, and fibrosis in animal models. We found that paroxetine suppressed sympathetic overdrive and increased the adrenergic receptor sensitivity to catecholamines. Paroxetine treatment also blocks epinephrine‐induced upregulation of hypertrophic and fibrotic genes as well as ADRB1 internalization in cardiomyocytes. Coadministration of paroxetine further potentiates metoprolol‐induced reductions in blood pressure and heart rate, further attenuating cardiac hypertrophy in spontaneously hypertensive rats. Furthermore, in patients with hypertension accompanied with depression, we observed that cardiac remodeling was less severe in those with paroxetine treatment compared with those with other types of anti‐depressive agents.ConclusionsParoxetine promotes ADRB1 sensitivity and attenuates cardiac hypertrophy partially via blocking GRK2‐mediated ADRB1 activation and internalization in the context of hypertension.

Unraveling the Mystery of Cold Stress-Induced Myocardial Injury.

Exposure to low ambient temperature imposes great challenge to human health. Epidemiological evidence has noted significantly elevated emergency admission and mortality rate in cold climate in many regions, in particular, adverse events in cardiovascular system. Cold stress is becoming one of the important risk factors for cardiovascular death. Through recent advance in echocardiography and myocardial histological techniques, both clinical and experimental experiments have unveiled that cold stress triggers a variety of pathological and pathophysiological injuries, including ventricular wall thickening, cardiac hypertrophy, elevated blood pressure, decreased cardiac function, and myocardial interstitial fibrosis. In order to examine the potential mechanism of action behind cold stress-induced cardiovascular anomalies, ample biochemical and molecular biological experiments have been conducted to denote a role for mitochondrial injury, intracellular Ca2+ dysregulation, generation of reactive oxygen species (ROS) and other superoxide, altered gene and protein profiles for apoptosis and autophagy, and increased adrenergic receptor sensitivity in cold stress-induced cardiovascular anomalies. These findings suggest that cold stress may damage the myocardium through mitochondrial injury, apoptosis, autophagy, metabolism, oxidative stress, and neuroendocrine pathways. Although the precise nature remains elusive for cold stress-induced cardiovascular dysfunction, endothelin (ET-A) receptor, endoplasmic reticulum (ER) stress, transient receptor potential vanilloid, mitochondrial-related protein including NRFs and UCP-2, ROS, Nrf2-Keap1 signaling pathway, Bcl-2/Bax, and lipoprotein lipase (LPL) signaling may all play a pivotal role. For myocardial injury evoked by cold stress, more comprehensive and in-depth mechanisms are warranted to better define the potential therapeutic options for cold stress-associated cardiovascular diseases.

КЛИНИЧЕСКОЕ И ПРОГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ЭКСТРАСИСТОЛИЧЕСКОЙ АРИТМИИ У БЕРЕМЕННЫХ БЕЗ СТРУКТУРНЫХ ПОРАЖЕНИЙ СЕРДЦА

Pregnancy is accompanied by physiological hemodynamic changes (an increase in circulating blood volume, stroke volume, cardiac output, heart rate), autonomic (an increase in plasma concentrations of catecholamines, an increase in the sensitivity of adrenergic receptors) and hormonal changes (an increase in the synthesis of estrogen, progesterone, prostaglandins, reninogen, angiotensin) ... All this can contribute to a change in the excitability, automatism and refractoriness of the myocardium, lead to the development and / or an increase in its electrophysiological inhomogeneity and, thus, provoke and / or aggravate the course of an already existing arrhythmia. This article will consider the relevance of the problem of the clinical and prognostic significance of extrasystolic arrhythmia in pregnant women without structural heart damage. The goal of increasing the efficiency of predicting the course of ventricular extrasystole without structural heart lesions in pregnant women at various periods of gestation in terms of thyroid and cardiovascular hormones will be proposed. The study of indicators of pregnancy hormones in pregnant women at different gestational periods with ventricular extrasystole without structural heart damage, the study of indicators of the sinus node, atrioventricular node and refractory periods of the cardiac conduction system in pregnant women is an urgent issue for research at the present time.

Impaired modulation of postjunctional α1 - but not α2 -adrenergic vasoconstriction in contracting forearm muscle of postmenopausal women.

Contraction-mediated blunting of postjunctional α-adrenergic vasoconstriction (functional sympatholysis) is attenuated in skeletal muscle of ageing males, brought on by altered postjunctional α1 - and α2 -adrenergic receptor sensitivity. The extent to which postjunctional α-adrenergic vasoconstriction occurs in the forearms at rest and during exercise in postmenopausal women remains unknown. The novel findings indicate that contraction-mediated blunting of α1 - (via intra-arterial infusion of phenylephrine) but not α2 -adrenergic (via intra-arterial infusion of dexmedetomidine) vasoconstriction was attenuated in postmenopausal women compared to young women. Additional important findings revealed that postjunctional α-adrenergic vasoconstrictor responsiveness at rest does not appear to be affected by age in women. Collectively, these results contribute to our understanding of local neurovascular control at rest and during exercise with age in women. Contraction-mediated blunting of postjunctional α-adrenergic vasoconstriction (functional sympatholysis) is attenuated in older males; however, direct confirmation of this effect remains unknown in postmenopausal women (PMW). The present study examined whether PMW exhibit augmented postjunctional α-adrenergic receptor vasoconstriction at rest and during forearm exercise compared to young women (YW). Eight YW (24±1years) and eight PMW (65±1years) completed a series of randomized experimental trials: (1) at rest, (2) under high flow (adenosine infusion) conditions and (3) during 6min of forearm exercise at relative (20% of maximum) and absolute (7kg) intensities. Phenylephrine (α1 -agonist) or dexmedetomidine (α2 -agonist) was administered during the last 3min of each trial to elicit α-adrenergic vasoconstriction. Forearm vascular conductance (FVC) was calculated from blood flow and blood pressure. Vasoconstrictor responsiveness was identified as the change in FVC (%) during α-adrenergic agonist infusions from baseline (resting trial) or from steady-state conditions (high flow and exercise trials). During resting and high flow trials, the %FVC during α1 - and α2 -agonist stimulation was similar between YW and PMW. During exercise, α1 -mediated vasoconstriction was blunted in YW vs. PMW at relative (-6±2% vs. -15±3%) and absolute (-4±2% vs. -14±5%) workloads, such that blood flow and FVC were lower in PMW (P<0.05 for all). Conversely, α2 -mediated vasoconstriction was similar between YW and PMW at relative (-22±3% vs. -22±4%; P>0.05) and absolute (-19±3% vs. -18±4%; P>0.05) workloads. Collectively, these findings demonstrate that despite similar α-adrenergic vasoconstrictor responsiveness at rest, PMW have a decreased ability to attenuate α1 -adrenergic vasoconstriction in contracting skeletal muscle.

Augmented Vascular α1‐Adrenergic Receptor Sensitivity in Humans with Chronic Kidney Disease

Patients with chronic kidney disease (CKD) have sympathetic overactivity and difficult‐to‐control hypertension. CKD patients also have exercise‐induced hypertension contributing to poor physical capacity. Our previous studies showed that CKD patients have augmented increases in blood pressure in response to the same degree of sympathetic activation during exercise, suggesting heightened neurovascular transduction of sympathetic nerve activity. We hypothesized that augmented vascular α1‐adrenergic receptor (α1‐AR) sensitivity contributes to the exaggerated vasoconstriction and blood pressure responses to sympathetic activation in CKD. In 28 CKD (Stage III and IV) patients and 11 matched Controls, we measured the degree of vasoconstriction of a dorsal hand vein in response to serial infusions of 10 doses (ranging 15–12,000 ng/min) of the selective α1‐AR agonist phenylephrine (PE) using a linear variable differential transformer with a movable central core to detect changes in vascular diameter. Vascular diameters were expressed as a % reduction from baseline maximum dilation, and plotted against PE dose concentrations in individual semi‐logarithmic dose‐response curves, and analyzed using a 5‐variable sigmoid dose‐response model. The natural log (ln) PE dose that produced a 50% maximal constriction (ED50) was calculated to reflect sensitivity to PE (i.e. α1‐AR sensitivity). CKD patients had a significantly lower PE ED50 compared to Controls (ln PE dose 5.15±0.30 vs 6.68±0.64 ng/min, p=0.022), demonstrating that CKD patients have heightened vasoconstriction in response to vascular α1 AR activation. CKD patients also had a significantly greater change in systolic blood pressure (SBP) during rhythmic hand grip exercise performed at 20% of maximum voluntary contraction compared to Controls (SBP +20.18±2.7 vs +10.43±1.74 mmHg, p=0.01), suggesting that augmented vascular α1‐AR sensitivity may contribute to increased neurovascular transduction and heightened exercise pressor responses in CKD. There was also a trend towards a positive linear correlation between estimated glomerular filtration rate (eGFR) and PE ED50. Augmented vascular α1‐AR sensitivity may contribute to increased neurovascular transduction and hypertension in CKD patients.Support or Funding InformationSupported by NIH HL‐098744, VA Merit I01CX001065, American Heart Association 15CSA24340001This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Effect of Chronic NO Synthase Inhibition on the Vasoactive and Structural Properties of Thoracic Aorta, NO Synthase Activity, and Oxidative Stress Biomarkers in Young SHR.

Although the role of nitric oxide (NO) in essential hypertension is still unclear, the effects of long-term NO deficiency have not yet been investigated during the critical juvenile period in spontaneously hypertensive rats (SHR). We aimed to analyze the effects of chronic NO synthase (NOS) inhibition on systolic blood pressure (sBP), vasoactivity, morphological changes and superoxide level in the thoracic aorta (TA), NOS activity in different tissues, and general biomarkers of oxidative stress in plasma of young SHR. Four-week-old SHR were treated with NG-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day, p.o.) for 4-5 weeks. L-NAME treatment induced a transient sBP increase only, and surprisingly, slightly inhibited endothelium-dependent relaxation of TA. Hereby, the inhibition of NOS activity varied from tissue to tissue, ranging from the lowest in the TA and the kidney to the highest in the brain stem. In spite of an increased sensitivity of adrenergic receptors, the maximal adrenergic contraction of TA was unchanged, which was associated with changes in elastin arrangement and an increase in wall thickness. The production of reactive oxygen species in the TA was increased; however, the level of selected biomarkers of oxidative stress did not change. Our findings proved that the TA of young SHR responded to chronic NO deficiency by the development of adaptive mechanisms on the functional (preserved NO-derived vasorelaxation, unincreased contraction) and molecular (preserved NOS activity) level.

A Rare Case of Supraventricular Tachycardia During Pregnancy and Successful Management in Crisis Situation with Electrical Cardioversion and Radiofrequency Ablation.

The occurrence of symptomatic maternal arrhythmias during pregnancy is a cause of concern for the well-being of both the mother and the fetus. In women of reproductive age, the commonest arrhythmia is paroxysmal supraventricular tachycardia (SVT). SVT in pregnancy is defined as any tachyarrhythmia with a heart rate greater than 120 beats/min [1]. There are no reliable data on the incidence of paroxysmal SVT in pregnant women. The incidence in the general population is 35 per 1,00,000 person-years [2]. Over half of these patients are asymptomatic. The main mechanism for the development of SVT is via reentry (atrioventricular nodal reentrant tachycardia in 60 % of cases and atrioventricular reentrant tachycardia in 30 % cases) [3]. Episodes of SVT occur with increased frequency during pregnancy particulary in third trimester. Proposed mechanisms include the hyperdynamic circulation, the altered hormonal milieu, increased circulating levels of catecholamines, increased adrenergic receptor sensitivity and increased maternal effective circulating volume causing atrial stretch [4, 5]. Potential risk factor for SVT in pregnancy is underlying congenital or structural heart disease [6]. In most cases, there is no history of heart disease. Physical treatment like sinus carotid massage or Valsalva maneuvers followed by drug therapy is tried in hemodynamically stable patients. In cases of failure of above measure or when there is hemodynamic compromise, electrical cardioversion or invasive method like radiofrequency ablation is justified, which may jeopardize the mother and her fetus. No large-scale studies or randomized control trials regarding safety of ECV in pregnancy and agents for successful cardioversion are available [7]. The recommendations published by American College of Cardiology/American Heart Association Task Force on Practice Guidelines/European Society of Cardiology Committee for Practice Guidelines are solely based on expert consensus [8]. We present a case of maternal SVT with hemodynamic instability which failed to respond to physical and drug therapy.

Blood Pressure Responses to Muscle Sympathetic Nerve Activity are Accentuated in Smokers

Smoking is a risk factor for hypertension and other cardiovascular diseases. It is unclear if the blood pressure (BP) response to sympathetic activity is altered in smokers. In this project, we examined the BP response to muscle sympathetic nerve activity (MSNA) in 18 smokers and 10 nonsmokers. BP (Finapres), heart rate, and MSNA (microneurography) were continuously recorded during 10 min of supine rest, and these variables were analyzed on a beat-by-by basis. Signal averaging was used to examine the responses in the mean arterial pressure (MAP) and heart rate for 15 sec according to the onset of the MSNA bursts. MAP in smokers was higher than that in nonsmokers (92.5±2.3 vs. 85.6±2.9 mmHg, P=0.02). MSNA in smokers was not significantly greater than that in nonsmokers (24.1±3.1 vs. 19.3±3.8 bursts/min, P>0.05). In the both groups, the averaged MSNA burst occurred in a nadir of the averaged MAP curve with ~1-2 sec time lag. Thereafter, MAP gradually increased, reaching a peak at ~6-8 sec following MSNA bursts. However, the MAP increase in smokers was significantly greater than that in nonsmokers (Δ2.94±0.71 vs. Δ1.58±0.31 mmHg, P<0.05). These data suggest that the BP response to the sympathetic activity may be accentuated in smokers. We speculate that altered adrenergic receptor sensitivity and/or baroreflex function may contribute to it.

Posturalinės ortostatinės tachikardijos sindromas

Orthostatic intolerance defines a group of symptoms characterized by cerebral hypo-perfusion and/or sympathetic activation that appear on standing upright and remit in the supine position. Patients may complain of headache, nausea, abdominal pain, light headedness, diminished concentration, syncope, anxiety, weakness, fatigue, exercise intolerance, palpitations, dyspepsia, and chest pain. POTS criteria: increased heart rate 30 beats/min or more contractions within the first 10 min of a change in the vertical position, there is no position-induced hypo-tension, orthostatic intolerance symptoms. POTS is the most common form of orthostatic intolerance. This is the most common syndrome among young people, who have autonomic dysfunction clinic. POTS patients ages - young, between 14 and 45 years. POTS ethology is heterogeneous. It was found that POTS can cause a variety of reasons, but which is primary and which are secondary - remains unclear. We assessed the case: 28 years old patient was hospitalized to Lithuanian University of Health Sciences Kaunas hospital for Abnormal nor epinephrine surgical treatment of oesophageal achalasia. The start of surgery clearance and adrenergic receptor sensitivity in idiopathic (laparoscopic cardiomiotomy) and gas insuffliation was madeorthostatic intolerance.without any complications. But when the patient‘s position was changed (reverse Tredelenburg) was monitorised atrial flutter (he-art rate 130 beats per minute, blood pressure 146/106 mmHg). For atrial flutter correction were used KCl, Mg SO4, and intravenous esmolol. After that, heart rate gradually decreased from 130 beats/ min to 92-80 beats/min. During all surgery, the patient‘s condition was stable, but a normal sinus rhythm observed at the end of operation, when the patient was returned to her primary position.There was a research in Mayo Clinic (Minnesota, USA) which objective - to investigate perioperative patients with postural orthostatic tachycardia syndrome (POTS) preparation, and to identify unexpected complications during operation. The research was conducted on the 152 patients to identify all surgical procedures performed during general anaesthesia between January 1, 1993 andDecember 31, 2006 at Mayo Clinic. There were selected 13 patients (12 women, 1 man) of 152. From research there was found that autonomic dysfunction associated with POTS may present unusual physiologic challenges in the perioperative period.

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Introduction: Ethnic differences in adrenergic receptor density and sensitivity has been suggested to play a key role in the response to antihypertensive cardiovascular drug therapy. The impact of ethnicity for the critically ill patient requiring cardiovascular drug support has not been described. Currently in the intensive care unit (ICU), ethnicity is not considered in the management of vasopressor (VP) therapy of septic shock patients. Hypothesis: VP requirements for septic shock patients in the ICU vary between two ethnic groups: African Americans (AA) and Caucasians (CA). Methods: A retrospective cohort study conducted in an urban, academic tertiary care center. Septic shock patients admitted from October 2008 to December 2010 were evaluated. Baseline demographics included age, gender, co-morbidities, source of infection, and APACHE II scores. VP dosing, duration, and mean (using hourly dose) were collected. Univariate analysis with Chi-square, Fisher’s exact test or t-test was performed. Results: 90 of 203 patients evaluated with septic shock requiring VP support initiated in the ICU were included. 54 (60%) patients were AA and 36 (40%) were CA. There were no significant differences in baseline demographics, except end stage renal disease in AA (P=0.001). The mean APACHE II score was 19.5 ± 5.8 for AA and 19.4 ± 7.7 for CA (P=0.9). Norepinephrine was used in 89%, vasopressin 37%, phenylephrine 27%, dopamine 8% and epinephrine 4% of patients. 59% of the patients required one VP, 24% required two VP and 17% required? 3 VP. There were no statistical differences in time to goal mean arterial pressure, fluid requirements or duration of VP therapy between AA and CA.For phenylephrine, higher starting (72.7 mcg/min vs. 25.5 mcg/min, P=0.03), maximum (238.7 mcg vs. 149.5 mcg, P=0.04), and mean (171.1 mcg vs. 90.4 mcg, P=0.02) doses were required in AA compared to CA, respectively. For norepinephrine, AA required a higher mean dose (23.4 mcg/min vs. 13.6 mcg/min, P=0.03) compared to CA. Conclusions: A significant ethnic-based variation in the requirements of phenylephrine and norepinephrine was found between AA and CA septic shock patients with no significant difference in vasopressor duration or fluid requirements.

Differential TNF production by monocyte subsets under physical stress: Blunted mobilization of proinflammatory monocytes in prehypertensive individuals

Elevated blood pressure (BP) and infiltration of the vasculature by monocytes contribute to vascular pathology; but, monocyte migratory characteristics based on differing inflammatory potential under adrenergic activation remains unclear. We compared nonclassical (CD14(+)CD16(++); HLA-DR(+)), intermediate (CD14(++)CD16(+); HLA-DR(++)), and classical (CD14(++)CD16(-); HLA-DR(+/-)) monocyte trafficking and their LPS-stimulated TNF production in response to a physical stressor (20-min treadmill exercise at 65-70% VO(2peak)) in participants with high prehypertension (PHT), mild PHT or normal BP (NBP). To determine adrenergic receptor (AR) sensitivity, pre-exercise cells were also treated with isoproterenol (Iso). When cells were stimulated with LPS, the CD16 molecules were downregulated, and monocyte subsets were differentiated based on HLA-DR expression. Monocyte subpopulations (as % of total monocytes) and intracellular TNF production were evaluated by flow cytometry. TNF production in all subsets decreased post-exercise and with ex-vivo incubation with Iso, irrespective of BP (p<0.001), with nonclassical and intermediate monocytes being a major source of TNF production. Overall, % nonclassical monocytes increased, % intermediate did not change, whereas % classical decreased post-exercise (p<0.001). However, % increase in nonclassical monocytes under exercise-induced adrenergic activation was blunted in high PHT individuals (p<0.05), but not in individuals with mild PHT and NBP. These findings extend our previous reports by showing that the mobilization of proinflammatory monocytes under physical stress is attenuated with even mild BP elevation. This may be indicative of monocytic AR desensitization and/or greater adhesion of "proinflammatory" monocytes to the vascular endothelium in hypertension with potential clinical implications of vascular pathology.

47. Differing trafficking and TNF-alpha production by monocyte subsets under adrenergic activation: Blunted mobilization of “pro-inflammatory” monocytes in individuals with elevated blood pressure

Elevated blood pressure (BP) and infiltration of the vasculature by monocytes contribute to vascular pathology; but, monocyte migratory characteristics based on differing inflammatory potential under adrenergic activation remains unclear. We compared “non-classical” (CD16++CD14+), “intermediate” (CD16+CD14++), and “classical” (CD16-CD14++) monocyte trafficking and their LPS-stimulated TNF-alpha production in response to a physical stressor (20-min treadmill exercise at 65–70% VO2peak) in participants ( n = 77) with high pre-hypertension (PHT), mild PHT or normal BP (NBP). To determine adrenergic receptor sensitivity, pre-exercise cells were also treated with isoproterenol (Iso) before LPS stimulation. Monocyte subpopulations and intracellular TNF-alpha production were evaluated by flow cytometry. Epinephrine and norepinephrine levels were significantly elevated during exercise. Overall, % non-classical monocytes increased, % intermediate did not change, whereas % classical decreased post-exercise ( p < .001). However, the % increase in non-classical monocytes under adrenergic activation was blunted in PHT individuals ( p < .05). TNF-alpha production in all subsets decreased post-exercise and with in-vitro Iso treatment, irrespective of BP ( p < .001), with nonclassical and intermediate monocytes being a major source of TNF-alpha production. These findings extend our previous reports by showing that the mobilization of “pro-inflammatory” monocytes under sympathoadrenal activation is attenuated with even mild BP elevation. This may be indicative of monocytic adrenergic receptor desensitization and/or greater adhesion of “pro-inflammatory” monocytes to the vascular endothelium in hypertension with clinical implications of vascular pathology.

α1‐Adrenergic responsiveness in human skeletal muscle feed arteries: the impact of reducing extracellular pH

Graded exercise results not only in the modulation of adrenergic mediated smooth muscle tone and a preferential increase in blood flow to the active skeletal muscle termed 'functional sympatholysis', but is also paralleled by metabolically induced reductions in pH. We therefore sought to determine whether pH attenuates α(1)-adrenergic receptor sensitivity in human feed arteries. Feed arteries (560 ± 31 μm i.d.) were harvested from 24 humans (55 ± 4 years old) and studied using the isometric tension technique. Vessel function was assessed using KCl, phenylephrine (PE), ACh and sodium nitroprusside (SNP) concentration-response curves to characterize non-receptor-mediated and receptor-mediated vasocontraction, as well as endothelium-dependent and -independent vasorelaxation, respectively. All concentration-response curves were obtained from (originally contiguous) vessel rings in separate baths with a pH of 7.4, 7.1, 6.8 or 6.5. Reduction of the pH, via HCl, reduced maximal PE-induced vasocontraction (pH 7.4 = 85 ± 19, pH 7.1 = 57 ± 16, pH 6.8 = 34 ± 15 and pH 6.5 = 16 ± 5% KCl(max)), which was partly due to reduced smooth muscle function, as assessed by KCl (pH 7.4 = 88 ± 13, pH 7.1 = 67 ± 8, pH 6.8 = 67 ± 9 and pH 6.5 = 58 ± 8% KCl(max)). Graded acidosis had no effect on maximal vasorelaxation. In summary, these data reveal that reductions in extracellular pH attenuate α(1)-mediated vasocontraction, which is partly explained by reduced smooth muscle function, although vasorelaxation in response to ACh and SNP remained intact. These findings support the concept that local acidosis is likely to contribute to functional sympatholysis and exercise hyperaemia by opposing sympathetically mediated vasoconstriction while not impacting vasodilatation.