RESUMEN
The prevalence of hypertension in non-Hispanic black (BL) individuals is the greatest of any racial/ethnic group. While 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 to 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. Herein, we are focused on emerging evidence indicating 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.
RESUMEN
PURPOSE: Evidence suggests that traditional low-frequency spinal cord stimulation (LF-SCS) reduces arterial blood pressure (BP) in patients with chronic pain and hypertension independent of improved pain symptoms. However, it remains unclear whether high-frequency spinal cord stimulation (HF-SCS) also lowers BP in chronic pain patients with hypertension. Therefore, in a retrospective study design, we tested the hypothesis that clinic BP would be significantly reduced following implantation of HF-SCS in patients with chronic pain and hypertension. METHODS: Clinic BP within 3 months before and after surgical implantation of either a LF-SCS or HF-SCS device between 2010 and 2020 were collected from electronic medical records at The University of Kansas Health System (TUKHS). RESULTS: A total of 132 patients had available records of clinic BP (64 ± 13 years of age). Patients with hypertension (n = 32) demonstrated a significantly greater reduction in systolic BP (-8 ± 12 versus 2 ± 9 mmHg, P < 0.001) following implantation compared with normotensive patients (n = 100). Importantly, the change in BP was inversely related to baseline BP independent of age and sex following implantation of HF-SCS (n = 70, R = -0.50, P < 0.001) or LF-SCS (n = 62, R = -0.42, P = 0.001). Higher pain scores before implantation were not associated with reduction in systolic BP (R = 0.10, P = 0.43) or diastolic BP (R = -0.08, P = 0.53) (n = 69) after implantation. CONCLUSION: These findings confirm previous studies showing reduced BP following implantation of LF-SCS in patients with chronic pain and hypertension and provide novel data regarding reduced BP following implantation of newer generation HF-SCS devices.
Asunto(s)
Dolor Crónico , Hipertensión , Estimulación de la Médula Espinal , Humanos , Dolor Crónico/terapia , Estudios Retrospectivos , Presión Arterial , Hipertensión/terapia , Médula Espinal , Resultado del TratamientoRESUMEN
The use of spontaneous bursts of muscle sympathetic nerve activity (MSNA) to assess arterial baroreflex control of sympathetic nerve activity has seen increased utility in studies of both health and disease. However, methods used for analyzing spontaneous MSNA baroreflex sensitivity are highly variable across published studies. Therefore, we sought to comprehensively examine methods of producing linear regression slopes to quantify spontaneous MSNA baroreflex sensitivity in a large cohort of subjects (n = 150) to support a standardized procedure for analysis that would allow for consistent and comparable results across laboratories. The primary results demonstrated that 1) consistency of linear regression slopes was considerably improved when the correlation coefficient was above -0.70, which is more stringent compared with commonly reported criterion of -0.50, 2) longer recording durations increased the percentage of linear regressions producing correlation coefficients above -0.70 (1 min = 15%, 2 min = 28%, 5 min = 53%, 10 min = 67%, P < 0.001) and reaching statistical significance (1 min = 40%, 2 min = 69%, 5 min = 78%, 10 min = 89%, P < 0.001), 3) correlation coefficients were improved with 3-mmHg versus 1-mmHg and 2-mmHg diastolic blood pressure (BP) bin size, and 4) linear regression slopes were reduced when the acquired BP signal was not properly aligned with the cardiac cycle triggering the burst of MSNA. In summary, these results support the use of baseline recording durations of 10 min, a correlation coefficient above -0.70 for reliable linear regressions, 3-mmHg bin size, and importance of properly time-aligning MSNA and diastolic BP. Together, these findings provide best practices for determining spontaneous MSNA baroreflex sensitivity under resting conditions for improved rigor and reproducibility of results.
Asunto(s)
Barorreflejo , Electrodiagnóstico/normas , Músculo Esquelético/inervación , Sistema Nervioso Simpático/fisiología , Adolescente , Adulto , Anciano , Presión Arterial , Femenino , Voluntarios Sanos , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de Tiempo , Estados Unidos , Adulto JovenRESUMEN
PURPOSE: Acute pain and resting arterial blood pressure (BP) are positively correlated in patients with chronic pain. However, it remains unclear whether treatment for chronic pain reduces BP. Therefore, in a retrospective study design, we tested the hypothesis that implantation of an epidural spinal cord stimulator (SCS) device to treat chronic pain would significantly reduce clinic pain ratings and BP and that these reductions would be significantly correlated. METHODS: Pain ratings and BP in medical records were collected before and after surgical implantation of a SCS device at the University of Iowa Hospitals and Clinics between 2008 and 2018 (n = 213). RESULTS: Reductions in pain rating [6.3 ± 2.0 vs. 5.0 ± 1.9 (scale: 0-10), P < 0.001] and BP [mean arterial pressure (MAP) 95 ± 10 vs. 89 ± 10 mmHg, P < 0.001] were statistically significant within 30 days of SCS. Interestingly, BP returned toward baseline within 60 days following SCS implantation. Multiple linear regression analysis showed that sex (P = 0.007), baseline MAP (P < 0.001), and taking hypertension (HTN) medications (P < 0.001) were significant determinants of change in MAP from baseline (Δ MAP) (model R2 = 0.33). After statistical adjustments, Δ MAP was significantly greater among women than among men ( - 7.2 ± 8.5 vs. - 3.9 ± 8.5 mmHg, P = 0.007) and among patients taking HTN medications than among those not taking hypertension medications ( - 10.1 ± 8.7 vs. - 3.9 ± 8.5 mmHg, P < 0.001), despite no group differences in change in pain ratings. CONCLUSIONS: Together, these findings suggest that SCS for chronic pain independently produces clinically meaningful, albeit transient, reductions in BP and may provide a rationale for studies aimed at reducing HTN medication burden among this patient population.
Asunto(s)
Dolor Crónico , Estimulación de la Médula Espinal , Presión Arterial , Dolor Crónico/terapia , Femenino , Humanos , Masculino , Estudios Retrospectivos , Médula Espinal , Resultado del TratamientoRESUMEN
Patients with type 2 diabetes (T2D) exhibit greater daytime blood pressure (BP) variability, increasing their cardiovascular risk. Given the number of daily activities that incorporate short-duration isometric muscle contractions (e.g., carrying groceries), herein we investigated BP and muscle sympathetic nerve activity (MSNA) responses at the onset of isometric handgrip (HG). We tested the hypothesis that, relative to control subjects, patients with T2D would exhibit exaggerated pressor and MSNA responses to the immediate onset of HG. Mean arterial pressure (MAP) and MSNA were quantified during the first 30 s of isometric HG at 30% and 40% of maximal voluntary contraction (MVC) and during a cold pressor test (CPT), a nonexercise sympathoexcitatory stimulus. The onset of 30% MVC HG evoked similar increases in MAP between groups (P = 0.17); however, the increase in MSNA was significantly greater in patients with T2D versus control subjects with the largest group difference at 20 s (P < 0.001). At the onset of 40% MVC HG, patients with T2D demonstrated greater increases in MAP (e.g., 10 s, T2D: 9 ± 1 mmHg, controls: 5 ± 2 mmHg; P = 0.04). MSNA was also greater in patients with T2D at 40% MVC onset but differences were only significant at the 20-30 s timepoint (T2D: 15 ± 3 bursts/min, controls: -2 ± 4 bursts/min; P < 0.001). Similarly, MAP and MSNA responses were augmented during the onset of CPT in T2D patients. These findings demonstrate exaggerated pressor and MSNA reactivity in patients with T2D, with rapid and robust responses to both isometric contractions and cold stress. This hyper-responsiveness may contribute to daily surges in BP in patients with T2D, increasing their short-term and long-term cardiovascular risk.
Asunto(s)
Presión Arterial , Diabetes Mellitus Tipo 2/fisiopatología , Contracción Isométrica , Músculo Esquelético/inervación , Reflejo , Sistema Nervioso Simpático/fisiopatología , Biomarcadores/sangre , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Missouri , Estudios Retrospectivos , Texas , Factores de TiempoRESUMEN
Aging is characterized by increased wall thickness of the central elastic arteries (i.e., aorta and carotid arteries), although the mechanisms involved are unclear. Evidence suggests that age-related increases in muscle sympathetic nerve activity (MSNA) may be a contributing factor. However, studies in humans have been lacking. Therefore, we tested the hypothesis that age-related increases in MSNA would be independently associated with carotid artery intima-media thickness (IMT) but not in young women given the reduced influence of MSNA on the vasculature in this group. In 93 young and middle-age/older (MA/O) adults (19-73 yr, 41 women), we performed assessments of MSNA (microneurography) and common carotid IMT and lumen diameter (ultrasonography). Multiple regression that included MSNA and other cardiovascular disease risk factors indicated that MSNA (P = 0.002) and 24-h systolic blood pressure (BP) (P = 0.024) were independent determinants of carotid IMT-to-lumen ratio (model R2 = 0.38, P < 0.001). However, when examining only young women (<45 yr), no correlation was observed between MSNA and carotid IMT-to-lumen ratio (R = -0.01, P = 0.963). MSNA was significantly correlated with IMT-to-lumen ratio while controlling for 24-h systolic BP among young men (R = 0.49, P < 0.001) and MA/O women (R = 0.59, P = 0.022). However, among MA/O men, controlling for 24-h systolic BP attenuated the association between MSNA and carotid IMT-to-lumen ratio (R = 0.50, P = 0.115). Significant age differences in IMT-to-lumen ratio between young and MA/O men (P = 0.047) and young and MA/O women (P = 0.023) were removed when adjusting for MSNA (men: P = 0.970; women: P = 0.152). These findings demonstrate an association between higher sympathetic outflow and carotid artery wall thickness with a particular exception to young women.NEW & NOTEWORTHY Increased wall thickness of the large elastic arteries serves as a graded marker for cardiovascular disease risk and progression of atherosclerosis. Findings from the present study establish an independent association between higher sympathetic outflow and carotid artery wall thickness in adults with an exception to young women and extend findings from animal models that demonstrate hypertrophy of vascular smooth muscle following chronic sympathetic-adrenergic stimulation.
Asunto(s)
Envejecimiento , Arterias Carótidas/fisiopatología , Enfermedades de las Arterias Carótidas/etiología , Músculo Esquelético/inervación , Nervio Peroneo/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Remodelación Vascular , Rigidez Vascular , Adulto , Factores de Edad , Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/fisiopatología , Grosor Intima-Media Carotídeo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores SexualesRESUMEN
Relative burst amplitude of muscle sympathetic nerve activity (MSNA) is an indicator of augmented sympathetic outflow and contributes to greater vasoconstrictor responses. Evidence suggests anxiety-induced augmentation of relative MSNA burst amplitude in patients with panic disorder; thus we hypothesized that acute stress would result in augmented relative MSNA burst amplitude and vasoconstriction in individuals with chronic anxiety. Eighteen participants with chronic anxiety (ANX; 8 men, 10 women, 32 ± 2 yr) and 18 healthy control subjects with low or no anxiety (CON; 8 men, 10 women, 39 ± 3 yr) were studied. Baseline MSNA and 24-h blood pressure were similar between ANX and CON ( P > 0.05); however, nocturnal systolic blood pressure % dipping was blunted among ANX ( P = 0.02). Relative MSNA burst amplitude was significantly greater among ANX compared with CON immediately preceding (anticipation) and during physiological stress [2-min cold pressor test; ANX: 73 ± 5 vs. CON: 59 ± 3% arbitrary units (AU), P = 0.03] and mental stress (4-min mental arithmetic; ANX: 65 ± 3 vs. CON: 54 ± 3% AU, P = 0.02). Increases in MSNA burst frequency, incidence, and total activity in response to stress were not augmented among ANX compared with CON ( P > 0.05), and reduction in brachial artery conductance during cold stress was similar between ANX and CON ( P = 0.92). Relative MSNA burst amplitude during mental stress was strongly correlated with state ( P < 0.01) and trait ( P = 0.01) anxiety (State-Trait Anxiety Inventory), independent of age, sex, and body mass index. Thus in response to acute stress, both mental and physiological, individuals with chronic anxiety demonstrate selective augmentation in relative MSNA burst amplitude, indicating enhanced sympathetic drive in a population with higher risk for cardiovascular disease. NEW & NOTEWORTHY Relative burst amplitude of muscle sympathetic nerve activity in response to acute mental and physiological stress is selectively augmented in individuals with chronic anxiety, which is a prevalent condition that is associated with the development of cardiovascular disease. Augmented sympathetic burst amplitude occurs with chronic anxiety in the absence of common comorbidities. These findings provide important insight into the relation between anxiety, acute stress and sympathetic activation.
Asunto(s)
Ansiedad/fisiopatología , Músculo Esquelético/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Adulto , Presión Sanguínea , Potenciales Evocados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/inervaciónRESUMEN
Evidence from animal studies indicates that hyperinsulinemia, without changes in glucose, increases ventilation via a carotid body-mediated mechanism. However, whether insulin elevates ventilation in humans independently of changes in glucose remains unclear. Therefore, we tested the hypothesis that insulin increases ventilation in humans during a hyperinsulinemic-euglycemic clamp in which insulin was elevated to postprandial concentrations while glucose was maintained at fasting concentrations. First, in 16 healthy young men ( protocol 1), we retrospectively analyzed respiration rate and estimated tidal volume from a pneumobelt to calculate minute ventilation during a hyperinsulinemic-euglycemic clamp. In addition, for a direct assessment of minute ventilation during a hyperinsulinemic-euglycemic clamp, we retrospectively analyzed breath-by-breath respiration rate and tidal volume from inspired/expired gasses in an additional 23 healthy young subjects ( protocol 2). Clamp infusion elevated minute ventilation from baseline in both protocols ( protocol 1: +11.9 ± 4.6% baseline, P = 0.001; protocol 2: +9.5 ± 3.8% baseline, P = 0.020). In protocol 1, peak changes in both respiration rate (+13.9 ± 3.0% baseline, P < 0.001) and estimated tidal volume (+16.9 ± 4.1% baseline, P = 0.001) were higher than baseline during the clamp. In protocol 2, tidal volume primarily increased during the clamp (+9.7 ± 3.7% baseline, P = 0.016), as respiration rate did not change significantly (+0.2 ± 1.8% baseline, P = 0.889). Collectively, we demonstrate for the first time in humans that elevated plasma insulin increases minute ventilation independent of changes in glucose.
Asunto(s)
Glucemia/metabolismo , Hiperinsulinismo/fisiopatología , Insulina/administración & dosificación , Pulmón/efectos de los fármacos , Ventilación Pulmonar/efectos de los fármacos , Adulto , Biomarcadores/sangre , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Hiperinsulinismo/sangre , Insulina/sangre , Pulmón/fisiopatología , Masculino , Estudios Retrospectivos , Factores de TiempoRESUMEN
NEW FINDINGS: What is the central question of this research? Does acute spinal cord stimulation increase vascular conductance and decrease muscle sympathetic nerve activity in the lower limbs of humans? What is the main finding and its importance? Acute spinal cord stimulation led to a rapid rise in femoral vascular conductance, and peroneal muscle sympathetic nerve activity demonstrated a delayed reduction that was not associated with the initial increase in femoral vascular conductance. These findings suggest that neural mechanisms in addition to attenuated muscle sympathetic nerve activity might be involved in the initial increase in femoral vascular conductance during acute spinal cord stimulation. ABSTRACT: Clinical cases have indicated an increase in peripheral blood flow after continuous epidural spinal cord stimulation (SCS) and that reduced muscle sympathetic nerve activity (MSNA) might be a potential mechanism. However, no studies in humans have directly examined the effects of acute SCS (<60 min) on vascular conductance and MSNA. In study 1, we tested the hypothesis that acute SCS (<60 min) of the thoracic spine would lead to increased common femoral vascular conductance, but not brachial vascular conductance, in 11 patients who previously underwent surgical SCS implantation for management of neuropathic pain. Throughout 60 min of SCS, common femoral artery conductance was elevated and significantly different from brachial artery conductance [in millilitres per minute: 15 min, change (Δ) 26 ± 37 versus Δ-2 ± 19%; 30 min, Δ28 ± 45 versus Δ0 ± 26%; 45 min, Δ48 ± 43 versus Δ2 ± 21%; 60 min, Δ36 ± 61 versus Δ1 ± 24%; and 15 min post-SCS, Δ51 ± 64 versus Δ6 ± 33%; P = 0.013]. A similar examination in a patient with cervical SCS revealed minimal changes in vascular conductance. In study 2, we examined whether acute SCS reduces peroneal MSNA in a subset of SCS patients (n = 5). The MSNA burst incidence in response to acute SCS gradually declined and was significantly reduced at 45 and 60 min of SCS (in bursts per 100 heart beats: 15 min, Δ-1 ± 12%; 30 min, Δ-14 ± 12%; 45 min, Δ-19 ± 16%; 60 min, Δ-24 ± 18%; and 15 min post-SCS: Δ-11 ± 7%; P = 0.015). These data demonstrate that acute SCS rapidly increases femoral vascular conductance and reduces peroneal MSNA. The gradual reduction in peroneal MSNA observed during acute SCS suggests that neural mechanisms in addition to attenuated MSNA might be involved in the acute increase in femoral vascular conductance.
Asunto(s)
Espacio Epidural/fisiología , Arteria Femoral/fisiología , Sistema Nervioso Simpático/fisiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/fisiología , Nervio Peroneo/fisiología , Estimulación de la Médula Espinal/métodosRESUMEN
NEW FINDINGS: What is the central question of this study? To understand better the effects of acute hyperglycaemia on arterial stiffness in healthy young individuals, we assessed arterial stiffness in physically active men before and after reduced ambulatory physical activity to decrease insulin sensitivity. What is the main finding and its importance? During an oral glucose tolerance test, we identified an increase in leg arterial stiffness (i.e. reduced femoral artery compliance) only when subjects were inactive for 5 days (<5000 steps day-1 ) and not when they were engaging in regular physical activity (>10,000 steps day-1 ). These results demonstrate the deleterious consequence of acute reductions in daily physical activity on the response of the peripheral vasculature to acute hyperglycaemia. ABSTRACT: Acute hyperglycaemia has been shown to augment indices of arterial stiffness in patients with insulin resistance and other co-morbidities; however, conflicting results exist in healthy young individuals. We examined whether acute hyperglycaemia after an oral glucose tolerance test (OGTT) increases arterial stiffness in healthy active men before and after reduced ambulatory physical activity to decrease insulin sensitivity. High-resolution arterial diameter traces acquired from Doppler ultrasound allowed an arterial blood pressure (BP) waveform to be obtained from the diameter trace within a cardiac cycle. In 24 subjects, this method demonstrated sufficient agreement with the traditional approach for assessing arterial compliance using applanation tonometry. In 10 men, continuous recordings of femoral and brachial artery diameter and beat-to-beat BP (Finometer) were acquired at rest, 60 and 120 min of an OGTT before and after 5 days of reduced activity (from >10,000 to <5000 steps day-1 ). Compliance and ß-stiffness were quantified. Before the reduction in activity, the OGTT had no effect on arterial compliance or ß-stiffness. However, after the reduction in activity, femoral compliance was decreased (rest, 0.10 ± 0.03 mm2 mmHg-1 versus 120 min OGTT, 0.06 ± 0.02 mm2 mmHg-1 ; P < 0.001) and femoral ß-stiffness increased (rest, 8.7 ± 2.7 a.u. versus 120 min OGTT, 15.3 ± 6.5 a.u.; P < 0.001) during OGTT, whereas no changes occurred in brachial artery compliance (P = 0.182) or stiffness (P = 0.892). Insulin sensitivity (Matsuda index) was decreased after the reduction in activity (P = 0.002). In summary, in young healthy men the femoral artery becomes susceptible to acute hyperglycaemia after 5 days of reduced activity and the resultant decrease in insulin sensitivity, highlighting the strong influence of daily physical activity levels on vascular physiology.
Asunto(s)
Arteria Braquial/fisiopatología , Arterias Carótidas/fisiología , Ejercicio Físico/fisiología , Arteria Femoral/fisiología , Glucosa/metabolismo , Rigidez Vascular/fisiología , Glucemia/metabolismo , Presión Sanguínea/fisiología , Arteria Braquial/metabolismo , Arterias Carótidas/metabolismo , Femenino , Arteria Femoral/metabolismo , Prueba de Tolerancia a la Glucosa/métodos , Humanos , Hiperglucemia/metabolismo , Hiperglucemia/fisiopatología , Insulina/metabolismo , Resistencia a la Insulina/fisiología , Masculino , Persona de Mediana Edad , Actividad Motora/fisiologíaRESUMEN
Previous studies have reported exaggerated increases in arterial blood pressure during exercise in type 2 diabetes (T2D) patients. However, little is known regarding the underlying neural mechanism(s) involved. We hypothesized that T2D patients would exhibit an augmented muscle metaboreflex activation and this contributes to greater pressor and sympathetic responses during exercise. Mean arterial pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were measured in 16 patients with T2D (8 normotensive and 8 hypertensive) and 10 healthy controls. Graded isolation of the muscle metaboreflex was achieved by postexercise ischemia (PEI) following static handgrip performed at 30% and 40% maximal voluntary contraction (MVC). A cold pressor test (CPT) was also performed as a generalized sympathoexcitatory stimulus. Increases in MAP and MSNA during 30 and 40% MVC handgrip were augmented in T2D patients compared with controls (P < 0.05), and these differences were maintained during PEI (MAP: 30% MVC PEI: T2D, Δ16 ± 2 mmHg vs. controls, Δ8 ± 1 mmHg; 40% MVC PEI: T2D, Δ26 ± 3 mmHg vs. controls, Δ16 ± 2 mmHg, both P < 0.05). MAP and MSNA responses to handgrip and PEI were not different between normotensive and hypertensive T2D patients (P > 0.05). Interestingly, MSNA responses were also greater in T2D patients compared with controls during the CPT (P < 0.05). Collectively, these findings indicate that muscle metaboreflex activation is augmented in T2D patients and this contributes, in part, to augmented pressor and sympathetic responses to exercise in this patient group. Greater CPT responses suggest that a heightened central sympathetic reactivity may be involved.
Asunto(s)
Presión Sanguínea , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Adulto , Presión Arterial , Frío , Ejercicio Físico , Femenino , Fuerza de la Mano , Frecuencia Cardíaca , Humanos , Isquemia , Contracción Isométrica , Masculino , Persona de Mediana Edad , Músculo Esquelético/inervación , PresiónRESUMEN
Despite greater blood pressure reactivity to acute cardiovascular stressors and a higher prevalence of hypertension in type 2 diabetes (T2D) patients, limited information is available regarding arterial baroreflex (ABR) control in T2D. We hypothesized that ABR control of muscle sympathetic nerve activity (MSNA) and heart rate (HR) are attenuated in T2D patients. Seventeen T2D patients (50 ± 2 yr; 31 ± 1 kg/m2), 9 weight-matched controls (WM-CON, 46 ± 2 yr; 32 ± 2 kg/m2) and 10 lean controls (Lean-CON, 49 ± 3 yr; 23 ± 1 kg/m2), underwent bolus infusions of sodium nitroprusside (100 µg) followed 60 s later by phenylephrine (150 µg) and weighted linear regression performed. No group differences in overall sympathetic baroreflex gain were observed (T2D: -2.5 ± 0.3 vs. WM-CON: -2.6 ± 0.2 vs. Lean-CON: -2.7 ± 0.4 arbitrary units·beat·mmHg-1, P > 0.05) or in sympathetic baroreflex gain when derived separately during blood pressure (BP) falls (nitroprusside) and BP rises (phenylephrine). In contrast, overall cardiac baroreflex gain was reduced in T2D patients compared with Lean-CON (T2D: 8.2 ± 1.5 vs. Lean-CON: 15.6 ± 2.9 ms·mmHg-1, P < 0.05) and also tended to be reduced in WM-CON (9.3 ± 1.9 ms·mmHg-1) compared with Lean-CON (P = 0.059). Likewise, during BP rises, cardiac baroreflex gain was reduced in T2D patients and weight-matched controls compared with lean controls (P < 0.05), whereas no group differences were found during BP falls (P > 0.05). Sympathetic and cardiac ABR gains were comparable between normotensive and hypertensive T2D patients (P > 0.05). These findings suggest preserved ABR control of MSNA in T2D patients compared with both obese and lean age-matched counterparts, with a selective impairment in ABR HR control in T2D that may be related to obesity.
Asunto(s)
Barorreflejo/efectos de los fármacos , Diabetes Mellitus Tipo 2/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Nitroprusiato/farmacología , Obesidad/fisiopatología , Fenilefrina/farmacología , Sistema Nervioso Simpático/efectos de los fármacos , Vasoconstrictores/farmacología , Vasodilatadores/farmacología , Adulto , Arterias/fisiopatología , Presión Sanguínea/efectos de los fármacos , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Músculo Esquelético/inervación , Obesidad/complicacionesRESUMEN
Several studies have demonstrated that blacks exhibit elevations in systemic oxidative stress. However, the source(s) and mechanism(s) contributing to the elevation in oxidative stress remain unclear. Given that peripheral blood mononuclear cells (PBMCs) can be a major source of NADPH oxidase-derived superoxide production, we tested the hypothesis that young black men demonstrate greater superoxide production and NADPH oxidase expression in PBMCs compared with whites. PBMCs were freshly isolated from whole blood in young normotensive black (n = 18) and white (n = 16) men. Intracellular superoxide production in PBMCs was measured using dihydroethidium fluorescence, protein expression of NADPH oxidase subunits, gp91(phox) (membranous) and p47(phox) (cytosolic) in PBMCs were assessed using Western blot analysis, and plasma protein carbonyls were measured as a marker of systemic oxidative stress. Black men showed elevated intracellular superoxide production (4.3 ± 0.5 vs. 2.0 ± 0.6 relative fluorescence units; black men vs. white men, P < 0.05), increased protein expression for gp91(phox) and p47(phox) (e.g., p47(phox): 1.1 ± 0.2, black men vs. 0.4 ± 0.1, white men, P < 0.05) in PBMCs and higher circulating protein carbonyl levels (22 ± 4 vs. 14 ± 2 nmol/ml; black men vs. white men, P < 0.05). Interestingly, a positive family history of hypertension in black men did not further enhance PBMC-derived intracellular superoxide production or NADPH oxidase subunit protein expression. These findings indicate that black men exhibit greater resting PBMC-derived superoxide production and an upregulation of the NADPH oxidase pathway with a possible contribution to increases in systemic oxidative stress.
Asunto(s)
Población Negra , Monocitos/metabolismo , Superóxidos/sangre , Voluntarios Sanos , Humanos , Hipertensión/etnología , Masculino , NADP/genética , NADP/metabolismo , Estrés Oxidativo , Carbonilación Proteica , Subunidades de Proteína/genética , Subunidades de Proteína/metabolismo , Población Blanca , Adulto JovenAsunto(s)
Hiperinsulinismo , Vasodilatación , Presión Sanguínea , Gasto Cardíaco , Humanos , VasoconstricciónRESUMEN
Type 2 diabetes mellitus patients (T2D) have elevated risk of stroke, suggesting that cerebrovascular function is impaired. Herein, we examined dynamic cerebral autoregulation (CA) at rest and during exercise in T2D patients and determined whether underlying systemic oxidative stress is associated with impairments in CA. Middle cerebral artery blood velocity and arterial blood pressure (BP) were measured at rest and during 2-min bouts of low- and high-intensity isometric handgrip performed at 20% and 40% maximum voluntary contraction, respectively, in seven normotensive and eight hypertensive T2D patients and eight healthy controls. Dynamic CA was estimated using the rate of regulation (RoR). Total reactive oxygen species (ROS) and superoxide levels were measured at rest. There were no differences in RoR at rest or during exercise between normotensive and hypertensive T2D patients. However, when compared with controls, T2D patients exhibited lower RoR at rest and during low-intensity handgrip indicating impaired dynamic CA. Moreover, the RoR was further reduced by 29 ± 4% during high-intensity handgrip in T2D patients (0.307 ± 0.012/s rest vs. 0.220 ± 0.014/s high intensity; P < 0.01), although well maintained in controls. T2D patients demonstrated greater baseline total ROS and superoxide compared with controls, both of which were negatively related to RoR during handgrip (e.g., total ROS: r = -0.71, P < 0.05; 40% maximum voluntary contraction). Collectively, these data demonstrate impaired dynamic CA at rest and during isometric handgrip in T2D patients, which may be, in part, related to greater underlying systemic oxidative stress. Additionally, dynamic CA is blunted further with high intensity isometric contractions potentially placing T2D patients at greater risk for cerebral events during such activities.
Asunto(s)
Circulación Cerebrovascular , Trastornos Cerebrovasculares/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/fisiopatología , Ejercicio Físico , Contracción Isométrica , Arteria Cerebral Media/fisiopatología , Presión Arterial , Velocidad del Flujo Sanguíneo , Estudios de Casos y Controles , Trastornos Cerebrovasculares/sangre , Trastornos Cerebrovasculares/diagnóstico , Trastornos Cerebrovasculares/etiología , Trastornos Cerebrovasculares/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/diagnóstico , Angiopatías Diabéticas/etiología , Angiopatías Diabéticas/metabolismo , Femenino , Fuerza de la Mano , Frecuencia Cardíaca , Homeostasis , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Estrés Oxidativo , Superóxidos/sangre , Factores de TiempoRESUMEN
Investigations of human myogenic responses typically use maneuvers that evoke robust changes in transmural pressure. Although this strategy has demonstrated peripheral myogenic responsiveness in the limbs, particularly in glabrous skin of the hand or foot, it has not considered the potential influence of the myogenic mechanism in beat-to-beat blood flow (BF) control during unprovoked rest. In the present study, we examined the interactions of spontaneous beat-to-beat mean arterial pressure (MAP; Finapres) with BF (Doppler ultrasound) supplying the forearm (brachial artery), lower leg (popliteal artery), and hand (ulnar artery) during 10 min of supine rest in healthy young men. Cross-correlation analyses revealed a negative association between MAP and BF, which was more prominent in the forearm than lower leg. The strongest correlation resulted when a -2-heart beat offset of MAP was applied (R=-0.53±0.04 in the forearm and -0.23±0.05 in the leg, P<0.05), suggesting an â¼2-s delay from instances of high/low MAP to low/high BF. Negatively associated episodes (high MAP/low BF and low MAP/high BF) outnumbered positively associated data (P<0.05). BF during low MAP values was greater than the steady-state average BF and vice versa. Wrist and ankle occlusion blunted the strength of correlations, homogenized the incidence of MAP and BF pairings, and reduced the magnitude of deviation from steady-state values. In contrast, these relationships were matched or accentuated for hand BF. Overall, these results suggest that myogenic responses are present and occur rapidly in human limbs during rest, overwhelm perfusion pressure gradient influences, and are primarily mediated by the distal limb circulation.
Asunto(s)
Presión Arterial , Arteria Braquial/fisiología , Antebrazo/irrigación sanguínea , Mano/irrigación sanguínea , Frecuencia Cardíaca , Extremidad Inferior/irrigación sanguínea , Arteria Poplítea/fisiología , Arteria Cubital/fisiología , Adulto , Velocidad del Flujo Sanguíneo , Arteria Braquial/diagnóstico por imagen , Homeostasis , Humanos , Masculino , Modelos Cardiovasculares , Arteria Poplítea/diagnóstico por imagen , Flujo Sanguíneo Regional , Descanso , Factores de Tiempo , Arteria Cubital/diagnóstico por imagen , Ultrasonografía DopplerRESUMEN
NEW FINDINGS: What is the central question of this study? The prevalence of sedentary behaviour in the workplace and increased daily sitting time have been associated with the development of cardiovascular disease; however, studies investigating the impact of sitting on vascular function remain limited. What is the main finding and its importance? We demonstrate that there is a marked vulnerability of the vasculature in the lower and upper limbs to prolonged sitting and highlight the importance of physical activity in restoring vascular function in a limb-specific manner. Sedentary behaviour in the workplace and increased daily sitting time are on the rise; however, studies investigating the impact of sitting on vascular function remain limited. Herein, we hypothesized that 6 h of uninterrupted sitting would impair limb micro- and macrovascular dilator function and that this impairment could be improved with a bout of walking. Resting blood flow, reactive hyperaemia to 5 min cuff occlusion (microvascular reactivity) and associated flow-mediated dilatation (FMD; macrovascular reactivity) were assessed in popliteal and brachial arteries of young men at baseline (Pre Sit) and after 6 h of uninterrupted sitting (Post Sit). Measures were then repeated after a 10 min walk (~1000 steps). Sitting resulted in a marked reduction of resting popliteal artery mean blood flow and mean shear rate (6 h mean shear rate, -52 ± 8 s(-1) versus Pre Sit, P < 0.05). Interestingly, reductions were also found in the brachial artery (6 h mean shear rate, -169 ± 41 s(-1) versus Pre Sit, P < 0.05). Likewise, after 6 h of sitting, cuff-induced reactive hyperaemia was reduced in both the lower leg (-43 ± 7% versus Pre Sit, P < 0.05) and forearm (-31 ± 11% versus Pre Sit, P < 0.05). In contrast, popliteal but not brachial artery FMD was blunted with sitting. Notably, lower leg reactive hyperaemia and FMD were restored after walking. Collectively, these data suggest that prolonged sitting markedly reduces lower leg micro- and macrovascular dilator function, but these impairments can be fully normalized with a short bout of walking. In contrast, upper arm microvascular reactivity is selectively impaired with prolonged sitting, and walking does not influence this effect.
Asunto(s)
Brazo/irrigación sanguínea , Arteria Braquial/fisiología , Postura/fisiología , Flujo Sanguíneo Regional/fisiología , Vasodilatación/fisiología , Adulto , Velocidad del Flujo Sanguíneo/fisiología , Humanos , Pierna/irrigación sanguínea , Masculino , Factores de TiempoRESUMEN
Recent work suggests that ß-adrenergic vasodilation offsets α-adrenergic vasoconstriction in young women, but this effect is lost after menopause. Given these age-related vascular changes, we tested the hypothesis that older women would exhibit a greater change in vascular conductance following baroreflex perturbation compared with young women. In 10 young (21 ± 1 yr) and 10 older (62 ± 2 yr) women, mean arterial pressure (MAP; Finometer), heart rate (HR), cardiac output (CO; Modelflow), total vascular conductance (TVC), and leg vascular conductance (LVC, duplex-Doppler ultrasound) were continuously measured in response to 5-s pulses of neck suction (NS; -60 Torr) and neck pressure (NP; +40 Torr) to simulate carotid hypertension and hypotension, respectively. Following NS, decreases in MAP were similar between groups; however, MAP peak response latency was slower in older women (P < 0.05). Moreover, at the time of peak MAP, increases in LVC (young, -11.5 ± 3.9%LVC vs. older, +19.1 ± 7.0%LVC; P < 0.05) and TVC were greater in older women, whereas young women exhibited larger decreases in HR and CO (young, -10 ± 3% CO vs. older, +0.8 ± 2% CO; P < 0.05). Following NP, increases in MAP were blunted (young, +14 ± 1 mmHg vs. older, +8 ± 1 mmHg; P < 0.05) in older women, whereas MAP response latencies were similar. Interestingly, decreases in LVC and TVC were similar between groups, but HR and CO (young, +7.0 ± 2% CO vs. older, -4.0 ± 2% CO; P < 0.05) responses were attenuated in older women. These findings suggest that older women have greater reliance on vascular conductance to modulate MAP via carotid baroreflex, whereas young women rely more on cardiac responsiveness. Furthermore, older women demonstrate a blunted ability to increase MAP to hypotensive stimuli.