Decreased Baroreflex Sensitivity Research Articles

LIPOPROTEIN ASSOCIATED PHOSPHOLIPASE A2 ACTIVITY IS NEGATIVELY ASSOCIATED WITH DECREASED BAROREFLEX SENSITIVITY IN HIGH NORMAL BLOOD PRESSURE

Objective: The relationship between baroreflex sensitivity (BRS) and inflammatory vascular biomarker Lipoprotein associated phospholipase A2 (Lp-PLA2) in subjects with high normal blood pressure (HNBP, prehypertensives) with a positive family history of hypertension (FHH+) to hypertension history free control subjects (FHH-) was evaluated. Design and method: A total of 24 HNBP participants (age 39.5 ± 2.5 years, 18 male/ 6 female) were studied. 14 HNBP subjects FHH+ were compared to 10 HNBP participants FHH-, being of similar age and body mass index. BRS (ms/mmHg) and BRSf (Hz/mmHg) were determined by the sequence and spectral methods (five-minute non-invasive beat-to-beat recording of blood pressure and inter-beat interval, controlled breathing at a frequency of 0.1 Hz). Venous blood was analysed for Lp-PLA2 biomarker of vascular inflammation and atherothrombotic activity. Results: A significant negative correlation between spontaneous BRS obtained by both methods and blood pressure (BP) was present (BRS spect r = –0.54, p<0.001, BRS seq r = –0.59, p<0.001). BRS obtained by sequence and spectral methods were reduced in HNBP FHH+ compared to group of HNBP without history of hypertension (P= 0.0317 BRS seq, P = 0.0395 BRS spect). There was no difference between both groups of HNBP subjects in BRSf values. Lp-PLA2 was significantly higher in HNBP FHH+ compared to FHH- controls (P = 0.025). Lp-PLA2 was negatively correlated with BRS obtained by sequence method (r = - 0.6758, P = 0.00028) and BRS obtained by spectral method (r = - 0.5935, P = 0.00031). Conclusions: Lipoprotein associated phospholipase A2 is negatively associated with decreased baroreflex sensitivity in subjects with high normal blood pressure and positive family history of hypertension. These findings demonstrate that reduced baroreflex sensitivity as marker of autonomic dysfunction is linked with vascular inflammation predominantly in otherwise healthy participants with positive history of hypertension that could predispose to increased risk of hypertension. Further research is needed.

Abstract 14951: Input From Renal Afferent Nerves Contributes to Hypertensive Heart Failure With Preserved Systolic Function Through Baroreflex Impairment and Sympathoexcitation

Introduction: Activation of renal afferent nerves, which can be caused by hypertensive renal damage, increases sympathetic output. The nucleus tractus solitarius (NTS) receives the inputs from baroreflex afferent nerves as well as renal afferent nerves. Baroreflex dysfunction leads to increased left ventricular (LV) end-diastolic pressure even in the heart with preserved systolic function. The GABAergic inhibitory system in the NTS blunts the signals from baroreflex afferent nerves, resulting in increased sympathetic output. Hypothesis: Input from renal afferent nerves contributes to hypertensive heart failure with preserved systolic function through baroreflex impairment and sympathoexcitation mediated by increased GABAergic inhibition in the NTS. Methods and Results: Male Dahl salt-sensitive rats with 8% high-salt diet from 7 weeks of age develop hypertensive HFpEF at 19 weeks. These rats underwent sham surgery (Sham), selective afferent renal denervation (ARDN), or additionally dissection of baroreflex afferent nerves (ARDN+BAROX) at 9 weeks. As controls, rats underwent sham surgery with a low-salt diet. The rats were evaluated at 19 weeks. Systolic blood pressure was similarly elevated in the three groups on high-salt diet. Impaired LV diastolic function assessed by echocardiography and pressure-volume loop analysis in Sham was recovered in ARDN group, while systolic function was preserved in all the group. Decreased baroreflex sensitivity and increased sympathetic output in Sham were attenuated in ARDN group. Activity of GABAergic neurons in the NTS evaluated by immunostaining was increased in Sham compared to controls, and was attenuated in ARDN group. All of the changes in ARDN were cancelled in ARDN+BAROX group. Conclusion: Input from renal afferent nerves contributes to hypertensive heart failure with preserved systolic function through baroreflex impairment and sympathoexcitation along with increased GABAergic inhibition in the NTS.

Cardiac Dysautonomia, Decreased Baroreflex Sensitivity and Increased Myocardial Workload in Patients with Chronic Spontaneous Urticaria: A Preliminary Report.

Chronic stress, a potential risk factor for cardiac autonomic dysfunction and cardiovascular (CV) risk, is known to induce the onset and exacerbation of chronic spontaneous urticaria (CSU), a psychodermatological disorder. However, data regarding CV risks due to the stress associated with CSU are very limited. This study aimed at comparing the cardiac sympathovagal balance (SVB), inflammatory markers, perceived stress and quality of sleep in patients with CSU (test group) and normal subjects (control group). In addition, it also aimed at assessing the correlation between the SVB and other study parameters in individuals with CSU. Thirty-four patients with CSU and twenty-eight age- and gender-matched healthy controls were recruited for the study. Heart rate variability (HRV), baroreflex sensitivity (BRS) and biochemical markers of stress and inflammation (s-cortisol, interleukin (IL)-6, IL-18 and high sensitivity C-reactive protein (hs-CRP)) were assessed following standard procedures. Perceived stress and sleep quality were assessed using pre-validated questionnaires. Study parameters were compared between the test and control groups using the independent-samples Student's t-test or Mann-Whitney U-test. The correlation between SVB and other study parameters was assessed using Spearman's rank correlation coefficient test. P < 0.05 was considered statistically significant. Levels of perceived stress, inflammatory markers, mean arterial pressure (MAP), myocardial workload (rate pressure product (RPP)), and HRV indices indicative of cardiac sympathetic activity were significantly high in individuals with CSU. In contrast, BRS and HRV indices indicative of parasympathetic activity and sleep quality were significantly low in these individuals. There was no significant correlation between SVB and other study parameters. Patients with CSU have cardiac dysautonomia characterised by increased sympathetic activity and decreased parasympathetic activity. Also, the reduced BRS and increased RPP point towards an increased risk of CV morbidity in these individuals.

Altered baroreflex sensitivity at rest and during Valsalva maneuver in healthy male offspring of hypertensive patients

A family history of hypertension puts young adults at a higher risk of developing hypertension, that too, at an earlier age than their parents. Recent studies suggest that the baroreflex mechanism, which takes care of the short-term regulation of blood pressure (BP), also plays a role in the long-term regulation of BP. Studies have reported decreased baroreflex sensitivity (BRS) in hypertensives. Reduced BRS is shown to herald the future occurrence of cardiovascular diseases (CVD) and helps in risk stratification AIM: Toassess BRS at rest and during the Valsalva maneuver among apparently healthy male offspring (age 18-35 years) of hypertensive patients. We recruited 37 participants whose parents (either/both) were hypertensive in the study group and whose parents (both) were not hypertensive in the control group. We measured basic anthropometric parameters (height, weight, waist circumference), cardiovascular parameters (heart rate and BP), short-term heart rate variability, and BRS (at rest and during Valsalva). We found that BRS at rest and BRS during the Valsalva maneuver were reduced among healthy male offspring of hypertensive parents than in healthy male offspring of non-hypertensive parents. Further, HRV indices and Valsalva ratio showed a sympathovagal imbalance in the form of decreased vagal and increased sympathetic activity. The reduced BRS and sympathovagal imbalance in male offspring of hypertensive parents reveal the early risk of developing hypertension in the future.

JS-HR-12: BASIC RESEARCH: ELUCIDATION OF “MOSAIC” PATHOGENESIS OF HYPERTENSION

Basic research plays critical roles in elucidating the “mosaic” pathogenesis of hypertension and developing its treatment. In the field of brain and autonomic nervous system, Chen et al. demonstrated that mild cold exposure elicits autonomic dysregulation, such as increased sympathetic activity and decreased baroreflex sensitivity, and poor sleep quality, causing blood pressure (BP) elevation in normotensive rats. This finding may have critical implications for the cardiovascular event occurrence with low ambient temperature. Domingos-Souza et al. showed that the ability of baroreflex activation to modulate hemodynamics and induce lasting vascular adaptation is critically dependent on the electrical parameters and duration of carotid sinus stimulation in spontaneously hypertensive rats (SHRs), proposing a rationale for improving baroreflex activation therapy in humans. In the kidney, Kasacka et al. showed that activity of Wnt/β-catenin pathway is increased in SHRs and 2K1C hypertensive rats, while it is inhibited in DOCA-salt rats. Intrarenal renin-angiotensin system (RAS) is involved in BP regulation. In renal damage with an impaired glomerular filtration barrier, liver-derived angiotensinogen filtered through damaged glomeruli regulates intrarenal RAS activity. Matsuyama et al. further showed that the glomerular filtration of liver-derived angiotensinogen depending on glomerular capillary pressure causes circadian rhythm of the intrarenal RAS. Otsuki et al. revealed that TWIST1, a transcription factor regulating mesodermal embryogenesis, transcriptionally upregulates complement 3, which has been demonstrated to activate intrarenal RAS, in the glomerular mesangial cells from SHRs. The RAS in the vascular system also contributes to BP regulation. Soring nexins (SNXs) are cellular sorting proteins and can regulate the expression and function of G protein-coupled receptors (GPCRs). Liu C et al. demonstrated that SNX1 knockout mice exhibit hypertension through vasoconstriction mediated by increased expression of GPCR AT1R within the arteries. Liu X et al. found that sirtuin 6 (SIRT6) expression is downregulated in the aortae of aged rats and showed that SIRT6 knockdown enhances angiotensin II-induced vascular adventitial aging by activating NF-κB pathway in vitro studies. The studies investigating extracellular vesicles (EVs) and gut microbiota have been increased. Ochiai-Homma et al. showed that pendrin in urinary EVs can be a useful biomarker for diagnosis and treatment of primary aldosteronism. Wu et al. demonstrated that captopril has the potential to rebalance the dysbiotic gut microbiota of DOCA-salt hypertensive rats. Several reports indicate the potential treatment for hypertension and the associated organ damages: rivaroxaban in cardiac hypertrophy; nebivolol, maximakinin, and Pinggan-Qianyang in hypertension; and melatonin and crocin in gestational hypertension.

Peripartum Cardiomyopathy Due to Gestational Hypertension and Tocolytic Therapy

Introduction: Peripartum cardiomyopathy (PPCM) is a rare and sometimes fatal systolic heart failure that affects women during late pregnancy or the early postpartum period. Risk factors contributing to this condition are: advanced maternal age, multiparity, administration of tocolytic agents, underlying cardiac disease, iatrogenic volume overload, preeclampsia, hypertension and In patients with gestational hypertension (GH) and other risk factors close monitoring is mandatory during pregnancy as well as in the postpartum period. Case report: A 38 year- old patient previously treated for endometriosis, infertility and GH was transferred from the Clinic of Gynecology due to diagnosed congestive heart failure. Five days prior admission she gave birth to her first child. Prior delivery she was treated with tocolytic therapy. She received methyldopa due to GH, that was abruptly discontinued after her delivery. Echocardiography on admission revealed moderately reduced left ventricular systolic function with an ejection fraction (EF) of 37% with dilated left ventricle (LV) and pulmonary artery hypertension (PAH) secondary to left ventricular failure. During hospitalization the patient was with signs of volume overload, but with well response on parenteral diuretic therapy. She was additionally treated with guideline recommended heart failure therapy. The controlled echocardiography showed improvement of the left ventricular function with an EF of 42%. Conclusion: PPCM is a rare condition with high morbidity and mortality. An LVEF &lt;30%, marked LV dilatation, LV end-diastolic diameter &gt;6.0 cm, and RV involvement are associated with adverse outcomes. Although delivery of the fetus and the placenta trigger resolution of symptoms and recovery to the nonpregnant state of various organism, the contrary happens with blood pressure. Its peaking time is three to six days after delivery. Hypertension medication must not be immediately terminated. Prolonged tocolytic therapy are a risk factor for PPCM due to causing decreased baroreflex sensitivity Patients with risk factors should be closely monitored for eventual cardiac complications.

Peripartum Cardiomyopathy Due to Gestational Hypertension and Tocolytic Therapy

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare and sometimes fatal systolic heart failure that affects women during late pregnancy or the early postpartum period. The risk factors contributing to this condition are advanced maternal age, multiparity, administration of tocolytic agents, underlying cardiac disease, iatrogenic volume overload, preeclampsia, and hypertension. In patients with gestational hypertension (GH) and other risk factors, close monitoring is mandatory during pregnancy as well as in the postpartum period. CASE REPORT: A 38-year-old patient previously treated for endometriosis, infertility, and GH was transferred from the clinic of gynecology due to diagnosed congestive heart failure. 5 days before admission, she gave birth to her first child. Before delivery, she was treated with tocolytic therapy. She received methyldopa due to GH which was abruptly discontinued after her delivery. Echocardiography on admission revealed moderately reduced left ventricular (LV) systolic function with an ejection fraction (EF) of 37% with dilated left ventricle (LV) and pulmonary artery hypertension secondary to LV failure. During hospitalization, the patient was with signs of volume overload, but with a good response on parenteral diuretic therapy. She was additionally treated with guideline-recommended heart failure therapy. The controlled echocardiography showed improvement of LV function with an EF of 42%. CONCLUSION: PPCM is a rare condition with high morbidity and mortality. An LVEF &lt;30%, marked LV dilatation, LV end-diastolic diameter &gt;6.0 cm, and RV involvement are associated with adverse outcomes. Although delivery of the fetus and the placenta triggers the resolution of symptoms and recovery to the nonpregnant state of various organisms, the contrary happens with blood pressure. Its peak time is 3–6 days after delivery. Hypertension medication must not be immediately terminated. Prolonged tocolytic therapy is a risk factor for PPCM due to causing decreased baroreflex sensitivity. Patients with risk factors should be closely monitored for eventual cardiac complications.

Decreased cognition is associated with altered cardiovascular autonomic functions and decreased baroreflex sensitivity in women with premenstrual syndrome

Premenstrual syndrome (PMS) is a clinical entity of concern in women of reproductive age group with its onset during the late luteal phase of the menstrual cycle that typically resolves within a few days after the onset of menstruation. Female reproductive hormones stimulate the gene promotor region of Gonadal steroids, which are modulators of the hypothalamic-pituitary axis, in association with the autonomic nervous system (ANS), form the stress system, which regulates the homeostatic mechanisms of the body. Disruption of this mechanism can lead to sympathovagal imbalance and cognitive deficits. Objectives: This study was aimed to compare the autonomic functions and cognition between PMS and control group. Methodology: This cross-sectional study was conducted as a pilot study with 20 subjects in each group. Autonomic function test and P300 were recorded. Study participants were also asked to answer Montreal cognitive assessment (MOCA) questionnaire. Results: On comparison of the test results between the two groups, individuals in PMS group were found to have increased sympathetic activity and reduced cognition when compared to the no PMS (control) group. Conclusion: The findings from this study proves a detrimental effect of gonadal steroids on autonomic nervous system and cognition.

Autonomic nervous system function in women with anorexia nervosa.

Abnormalities in autonomic function have been observed in people with anorexia nervosa. However, the majority of investigations have utilised heart rate variability as the sole assessment of autonomic activity. The current study utilised a variety of methodologies to assess autonomic nervous system function in women with a current diagnosis of anorexia, a past diagnosis of anorexia who were weight-restored, and healthy controls. The sample included 37 participants: 10 participants with anorexia, 17 weight-restored participants (minimum body mass index > 18.5 for minimum of 12months) and 10 controls. Assessments of autonomic function included muscle sympathetic nerve activity (MSNA) using microneurography, heart rate variability, baroreflex sensitivity, blood pressure variability, head-up tilt table test, sudomotor function and assessment of plasma catecholamines. MSNA (bursts/min) was significantly decreased in both anorexia (10.22 ± 6.24) and weight-restored (17.58 ± 1.68) groups, as compared to controls (23.62 ± 1.01, p < 0.001 and p = 0.033, respectively). Participants with anorexia had a significantly lower standard deviation in heart rate, lower blood pressure variability and decreased sudomotor function as compared to controls. Weight-restored participants demonstrated decreased baroreflex sensitivity in response to head-up tilt as compared to controls. Women with a current or previous diagnosis of anorexia have significantly decreased sympathetic activity, which may reflect a physiological response to decreased energy intake. During the state of starvation, women with anorexia also displayed decreased sudomotor function. The consequences of a sustained decrease in MSNA are unknown, and future studies should investigate autonomic function in long-term weight-restored participants to determine whether activity returns to normal.

Exaggerated Exercise Blood Pressure as a Marker of Baroreflex Dysfunction in Normotensive Metabolic Syndrome Patients

IntroductionExaggerated blood pressure response to exercise (EEBP = SBP ≥ 190 mmHg for women and ≥210 mmHg for men) during cardiopulmonary exercise test (CPET) is a predictor of cardiovascular risk. Sympathetic hyperactivation and decreased baroreflex sensitivity (BRS) seem to be involved in the progression of metabolic syndrome (MetS) to cardiovascular disease.ObjectiveTo test the hypotheses: (1) MetS patients within normal clinical blood pressure (BP) may present EEBP response to maximal exercise and (2) increased muscle sympathetic nerve activity (MSNA) and reduced BRS are associated with this impairment.MethodsWe selected MetS (ATP III) patients with normal BP (MetS_NT, n = 27, 59.3% males, 46.1 ± 7.2 years) and a control group without MetS (C, n = 19, 48.4 ± 7.4 years). We evaluated BRS for increases (BRS+) and decreases (BRS−) in spontaneous BP and HR fluctuations, MSNA (microneurography), BP from ambulatory blood pressure monitoring (ABPM), and auscultatory BP during CPET.ResultsNormotensive MetS (MetS_NT) had higher body mass index and impairment in all MetS risk factors when compared to the C group. MetS_NT had higher peak systolic BP (SBP) (195 ± 17 vs. 177 ± 24 mmHg, P = 0.007) and diastolic BP (91 ± 11 vs. 79 ± 10 mmHg, P = 0.001) during CPET than C. Additionally, we found that MetS patients with normal BP had lower spontaneous BRS− (9.6 ± 3.3 vs. 12.2 ± 4.9 ms/mmHg, P = 0.044) and higher levels of MSNA (29 ± 6 vs. 18 ± 4 bursts/min, P < 0.001) compared to C. Interestingly, 10 out of 27 MetS_NT (37%) showed EEBP (MetS_NT+), whereas 2 out of 19 C (10.5%) presented (P = 0.044). The subgroup of MetS_NT with EEBP (MetS_NT+, n = 10) had similar MSNA (P = 0.437), but lower BRS+ (P = 0.039) and BRS− (P = 0.039) compared with the subgroup without EEBP (MetS_NT−, n = 17). Either office BP or BP from ABPM was similar between subgroups MetS_NT+ and MetS_NT−, regardless of EEBP response. In the MetS_NT+ subgroup, there was an association of peak SBP with BRS− (R = −0.70; P = 0.02), triglycerides with peak SBP during CPET (R = 0.66; P = 0.039), and of triglycerides with BRS− (R = 0.71; P = 0.022).ConclusionNormotensive MetS patients already presented higher peak systolic and diastolic BP during maximal exercise, in addition to sympathetic hyperactivation and decreased baroreflex sensitivity. The EEBP in MetS_NT with apparent well-controlled BP may indicate a potential depressed neural baroreflex function, predisposing these patients to increased cardiovascular risk.

Arterial hypertension and bone health—a literature review

The prevalence of hypertension (AH) and osteoporosis is increasing worldwide, which is associated primarily with an increase in the proportion of people over the age of 50. A number of researchers have suggested that the two diseases share a common etiopathogenesis associated with low intake and correspondingly low serum calcium levels, vitamin D and vitamin K deficiency, and deviations in nitric oxide levels. In addition, there are additional prerequisites for the adverse effects of AH on bone tissue. It is known, for example, that higher blood pressure (BP) levels cause greater loss of calcium in the urine. On the other hand, AH is also associated with increased sympathetic tone, vascular disorders, abnormal cytokine levels, and increased activity of the renin-angiotensin-aldosterone system (RAAS) at the systemic and local levels. In addition, the number of falls, which are a leading factor in the occurrence of fractures, in patients with AH may be increased. A prerequisite for this is the presence of syncope associated with decreased baroreflex sensitivity or orthostatic hypotension caused by antihypertensive drugs. The potential link between AH and bone health has long been discussed, but the results of numerous clinical trials remain mixed. The presence of some inconsistencies in the literature may be related to differences in the stage and severity of AH among the studied populations, as well as to the control of AH. On the other hand, antihypertensive drugs, which have specific effects on different target organs, may further modulate bone homeostasis. However, not all studies clarify whether patients receive therapy for elevated AH.

Attenuation of baroreflex sensitivity and heart rate variability is linked to reduced levels of nitric oxide in pregnant women having risks of developing gestational hypertension

ABSTRACT Purpose: Decreased baroreflex sensitivity (BRS) and sympathovagal imbalance (SVI) have been reported as a cardiovascular (CV) risk in gestational hypertension (GH). Nitric oxide (NO) has been implicated in pathophysiology of GH. In the present study, we assessed the link of CV risks (decreased BRS and SVI) to the plasma levels of NO in women having risk of developing GH. Materials and Methods: A total of 96 pregnant women having risk factors for GH were recruited for the study. The blood pressure variability (BPV), heart rate variability (HRV), plasma NO, marker of insulin resistance (HOMA-IR), lipid risk factors, inflammatory markers (hsCRP, interleukin-6), and malondialdehyde (MDA), the marker of oxidative stress (OS) were measured at 16th and 36th week. Link of various parameters to NO was assessed by correlation and multiple regression analysis. Results: Of HRV indices, parasympathetic components were decreased and sympathetic components were increased, BRS was decreased, NO was decreased, HOMA-IR, lipid risk factors, hsCRP, interleukin-6, and MDA were increased significantly at 36th week compared to 16th week of pregnancy. Most of the markers of cardiometabolic risk were correlated with NO. However, only the markers of CV risk (SVI and reduced BRS) were independently associated with decreased level of NO, but not the metabolic markers except interleukin-6. The independent contribution of BRS (β = 0.334, P < .001) to NO was found to be most significant. Conclusion: It was concluded that decreased BRS, SVI, and increased interleukin-6 are associated with reduction in NO in GH, which may possibly be linked to the development of CV risks in GH.

Decreased baroreflex sensitivity is associated with cardiometabolic risks and prehypertension status in early-postmenopausal women

ABSTRACT Objective We studied the link of decreased baroreflex sensitivity (BRS) to cardiometabolic risks and prehypertension status in postmenopausal women during their early menopausal phase. Methods Premenopausal women (n = 55) and early-postmenopausal women (n = 50) of age group between 40 and 55 years were recruited for the study, and their anthropometric parameters, complete battery of autonomic function tests (AFT), BRS, hormone levels, and cardiometabolic risk parameters were measured and compared between two groups. Correlation analysis of BRS with various physiological and biochemical parameters in these two groups were performed. Multiple regression analysis of BRS with various other associated factors in postmenopausal subjects and bivariate logistic regression analysis for assessing prediction of prehypertension status by BRS in postmenopausal group were performed. Results There was a significant difference in AFT and metabolic parameters between premenopausal and postmenopausal women. Sympathovagal imbalance (increased sympathetic and decreased parasympathetic) was prominent in early-postmenopausal women. Decreased BRS, the marker of cardiovascular (CV) risk was found to be significant (P < .001) and correlated with various cardiometabolic parameters in early-postmenopausal subjects. Multiple regression analysis demonstrated that decreased BRS is independently linked to parameters of decreased vagal activity, inflammation, and oxidative stress in early-postmenopausal group. Decreased BRS could predict prehypertension status in early-postmenopausal subjects as confirmed by bivariate logistic regression analysis. Conclusion Sympathovagal imbalance, decreased BRS and considerable metabolic derangements were observed in women in their early phase of menopause. Decreased BRS appears to be associated with the cardiometabolic risks in these women. Prehypertension status in early-postmenopausal subjects could be predicted by decreased BRS.

ACTH Infusion Impairs Baroreflex Sensitivity-Implications for Cardiovascular Hypoglycemia-Associated Autonomic Failure.

Hypoglycemia attenuates cardiovascular homeostatic autonomic control. This attenuation, known as the cardiovascular component of hypoglycemia-associated autonomic failure (HAAF), is characterized most notably by decreased baroreflex sensitivity (BRS) that begins during hypoglycemia and persists until at least the next day, despite return to euglycemia. Understanding the mechanisms underlying this reduction in BRS is important because BRS attenuation is associated with increased morbidity and mortality. The objective of this work is to investigate the role of the adrenocorticotropin (ACTH)-adrenal axis in decreasing BRS. We tested the hypothesis that infusion of ACTH 1-24 (cosyntropin), as compared to placebo, would acutely suppress BRS, and that this decrease in BRS would be present the next day. A double-blind, placebo-controlled, random-order, cross-over study was conducted. This study took place in a clinical research center. Participants included healthy men and women. Interventions included an intravenous infusion of cosyntropin (70 μg/hour for 2.5 hours in the morning and again in the early afternoon) vs normal saline placebo. Outcome measures included BRS during and 16 hours after cosyntropin vs placebo infusions. Cosyntropin infusion attenuated BRS (mm Hg/ms) as compared to placebo (baseline 17.8 ± 1.38 vs 17.0 ± 2.07; during 14.4 ± 1.43 vs 17.3 ± 1.65; and next day 14.8 ± 1.42 vs 18.9 ± 2.04; P < .05, time by treatment, analysis of variance). BRS was decreased during the final 30 minutes of the morning cosyntropin infusion as compared to baseline (P < .01) and remained suppressed the next day (16 hours after afternoon infusion) (P < .025). Placebo infusion did not significantly change BRS. Corrected QT interval was not affected. ACTH attenuates BRS, raising the possibility that hypoglycemia-induced increases in ACTH may contribute to the cardiovascular component of HAAF.

Type 2 Diabetes Mellitus Is Independently Associated With Decreased Neural Baroreflex Sensitivity: The Paris Prospective Study III.

Impaired baroreflex function is an early indicator of cardiovascular autonomic imbalance. Patients with type 2 diabetes mellitus (T2D) have decreased baroreflex sensitivity (BRS), however, whether the neural BRS (nBRS) and mechanical component of the BRS is altered in those with high metabolic risk (HMR, impaired fasting glucose and metabolic syndrome) or with overt T2D, is unknown. We examined this in a community-based observational study, the Paris Prospective Study III (PPS3). Approach and Results: In 7626 adults aged 50 to 75 years, resting nBRS (estimated by low-frequency gain, from carotid distension rate and RR [time elapsed between two successive R waves] intervals) and mechanical BRS were measured by high-precision carotid echotracking. The associations between overt T2D or HMR as compared with subjects with normal glucose metabolism and nBRS or mechanical BRS were quantified using multivariable linear regression analysis. There were 319 subjects with T2D (61±6 years, 77% male), 1450 subjects with HMR (60±6 years, 72% male), and 5857 subjects with normal glucose metabolism (59±6 years, 57% male). Compared with normal glucose metabolism, nBRS was significantly lower in HMR subjects (β=-0.07 [95% CI, -0.12 to -0.01]; P=0.029) and in subjects with T2D (β=-0.18 [95% CI, -0.29 to -0.07]; P=0.002) after adjustment for confounding and mediating factors. Subgroup analysis suggests significant and independent alteration in mechanical BRS only among HMR patients who had both impaired fasting glucose and metabolic syndrome. In this community-based study of individuals aged 50 to 75, a graded decrease in nBRS was observed in HMR subjects and patients with overt T2D as compared with normal glucose metabolism subjects.

Hypoxic Training Is Beneficial in Elite Athletes.

There is no doubt that many hypoxic conditions or prolonged exposures to altitude result in “biological costs of hypoxic adaptations that outweigh their benefits” (1), particularly in endurance athletes exposed to a) exercise-induced arterial hypoxemia leading to a larger decrease in VO2max and aerobic endurance; b) increased sympathetic activity and decreased baroreflex sensitivity; and c) increased pulmonary arterial pressure. There is also no doubt that sleeping in moderate altitude (2000-3000 m) as performed by the athletes using either live high-train high (LHTH) or live high-train low (LHTL) methods leads to periodic breathing, intermittent hypoxia (IH) and increase in desaturation periods; e.g. 3% oxygen desaturation index, but to a larger extent in hypobaric hypoxia (HH, real altitude) than in normobaric hypoxia (NH, simulated altitude), as shown at 2250 m (2). The three main questions debated in the present contrasting perspective are however different: 1. Are there any evidences showing if the “counteracting maladaptation” (reported above) outweigh the benefits of the different hypoxic methods at short- or long-term in elite athletes? ; 2. Are there any robust data supporting that hypoxic training is beneficial in elite athletes? ; 3. Contradictory, are there robust data showing that hypoxic training is not beneficial in elite athletes?

Sympathovagal Imbalance, Decreased Baroreflex Sensitivity and Increased Myocardial Work Stress in Pregnant Women with Risk of Developing Gestational Hypertension: A Preliminary Report

Background and Aim: Though the mechanisms responsible for the pathogenesis of Gestational Hypertension (GHT) are unclear, it has been reported that the disease is characterized by low circulating volume and high vascular resistance. The increased peripheral vascular resistance is caused due to sympathetic overactivity which in turn causes the increase in blood pressure and Cardiovascular risk (CV). Therefore, in the present study, we aimed to study the sympathovagal imbalance, Baroreflex Sensitivity (BRS) and Rate Pressured Product (RPP) in pregnant women with risk of developing GHT during their first and third trimesters of gestation. Methods: Heart Rate (HR), Systolic and Diastolic Blood Pressure (SBP, DBP) were measured. Rate-pressure product was calculated using SBP and HR. Spectral analysis of Heart Rate Variability (HRV), Blood Pressure Variability (BPV) including BRS were assessed in a group of pregnant women (n=18) with risk factors for GHT at 16th week and 36th week of their gestation. Parameters were compared after 36th week with 16th weeks and analyzed. Results: It was observed that the ratio of low-frequency to high-frequency power (LF-HF ratio) of HRV was significantly increased at 36th week of pregnancy compared with 16th week. There was decreased BRS at 36th week of pregnancy in risk of GHT. Significant increase in RPP was seen at 36th week of pregnant women with risk of developing GHT when compared with 16th of gestation. Conclusion: In the present study we conclude that there is sympathovagal imbalance in pregnant women with risk of developing GHT. Also reduced BRS and increased RPP were seen in these subjects indicating that there was increased CV risk in these patients.

Time Course of Hemodynamic Responses to Different Doses of Lipopolysaccharide in Unanesthetized Male Rats.

Lipopolysaccharide (LPS) administration is a well-known method to induce systemic inflammation widely used for investigating new therapeutic strategies for sepsis treatment, which is characterized by clinical manifestations such as tachycardia and hypotension. However, there are different doses of LPS used in several studies, and the hemodynamic responses were not always well characterized. Thus, the present study aimed to evaluate the arterial pressure, heart rate, heart rate variability, and baroreflex function from rats, over time, to different doses of LPS. Femoral artery and vein catheters were inserted into anesthetized Wistar-Hannover male rats for arterial pressure recording and LPS administration, respectively. On the next day, the arterial pressure was recorded before and after (90, 180, and 360 min) LPS injection (0.06, 20, 30, and 40 mg/kg). All doses of LPS tested increased the heart rate and decreased baroreflex sensitivity over time. In addition, while LPS administration of 20, 30, and 40 mg/kg increased the mean arterial pressure over time, 0.06 mg/kg decreased the mean arterial pressure at 360 min, as compared to baseline values. Furthermore, high doses of LPS decreased the power of the HF band of the cardiac interval spectrum over time, and the higher dose increased the power of the LF band. Our data indicate that high doses of LPS promote hypertensive response over time, while a low dose decreases arterial pressure. Moreover, the changes in heart rate variability and baroreflex function elicited by LPS may be not associated with arterial pressure response produced by the endotoxemia.

Exposure to environmentally relevant concentration of second hand smoke increased blood pressure and decreased baroreflex sensitivity in mice

BACKGROUNDSecond hand smoke (SHS), a main indoor air pollution, is a significant risk factor for cardiovascular morbidity and mortality. Epidemiological studies link SHS exposure to increased sympathetic nerve activity (SNA) and blood pressure (BP), suggesting a central component in SHS‐induced cardiovascular dysregulation. However, we have limited information on effects of SHS on baroreflex sensitivity (BRS), an indicator of central regulation of BP and a stronger link to cardiovascular morbidity and mortality than the elevated BP. Additionally, we lack information on whether exposure to environmentally relevant levels of SHS affects BP regulation. Here we sought to test the hypothesis that chronic exposure to an environmentally relevant level of SHS elevates BP and reduces BRS.METHODSAdult male C57BL/6J mice (11 wk old) were implanted with BP/ECG telemetry devices. After two weeks of recovery from surgery, mice were randomly assigned to either filtered air (FA, n=18) or SHS (n=14) for up to 12 weeks. The SHS exposure level was similar to that of a smoky bar (3 mg/m3, 6 hr/d, 5 d/wk). 36 hours of continuous BP and ECG recordings were performed after the 5th day of exposure each week. Data were divided into three 12‐hr periods based on light cycle: dark 1, light and dark 2. Standard deviation of beat‐to‐beat BP was taken as the BP variability (BPV). BRS was determined with the sequence method using systolic BP.RESULTSThere was no difference in body weight between FA‐ and SHS‐exposed mice over the 12‐wk period. SHS exposure had no effect on dark‐light difference in BP, BPV, and BRS. Comparing to FA mice, SHS mice had higher systolic BP (~2.4 mmHg, p &lt; 0.05), mean BP (~3 mmHg, p &lt;0.05), and diastolic BP (~4 mmHg, p &lt; 0.05) by 4 weeks of exposure. SHS reduced pulse pressure (PP, ~2 mmHg, p &lt; 0.05), although the magnitude of the reduction diminished over time. In contrast, the SHS‐induced reduction in BRS was time dependent and accumulative, having a slower onset than changes in BP and PP, and becoming more severe with increasing exposure duration (−0.8%, −6.2%, and −12.3% for 4, 8, and 12 wk, respectively). SHS did not change BP variability, regardless of exposure duration.CONCLUSIONSThe effect of SHS on increased BP was observed after 4 wk of exposure and sustained through 12 wk of exposure. In contrast, SHS‐induced reductions in BRS showed a delayed onset that accumulates with prolonged exposures. The data suggest that SHS may activate multiple mechanisms resulting in BP dysregulation.Support or Funding InformationR01 ES025229This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Arterial baroreflex sensitivity: Relationship with peripheral chemoreflex in patients with chronic heart failure

BackgroundThe purpose of this study was to evaluate the relationship between the breath-holding duration and the sensitivity of the arterial baroreflex, as well as the prognostic value of the breath-holding test in the assessment of decreased baroreflex sensitivity (BRS) in patients with chronic heart failure (CHF). MethodsThe study was conducted on 87 patients with CHF. In all participants, the breath-holding test was performed in the morning, while the single-breath carbon dioxide test was performed on the next day; the injection method was used to evaluate BRS. Other parameters, including pulse wave velocity (PWV), N-terminal pro-brain natriuretic peptide (NT-proBNP) level, and spirometry and echocardiography findings, were also evaluated. ResultsA significant correlation was found between BRS and the following two parameters: breath-holding duration and left ventricular ejection fraction (all p < 0.05) and a significant negative correlation between BRS and the following three parameters: age, NT-proBNP level, and PWV (all p < 0.05). After analysis, only the breath-holding duration remained significant in our model (R2 adjusted for the model, 0.55). The breath-holding duration was a good predictor of decreased BRS (<3 ms/mmHg), with a cut-off point of <34 s [area under curve, 0.876 (0.778–0.937, p < 0.0001)]. ConclusionA reduced breath-holding duration is associated with decreased sensitivity of the arterial baroreflex. If the duration of the breath-holding test is <34 s, decreased BRS is predicted. This test can be effectively used for the initial assessment of the level of the reflex regulation of the cardiorespiratory system in patients with CHF.