Sympathetic Vasoconstrictor Responses Research Articles

Estrogen, Exercise Training, and Nitric-oxide Mediated Sympatholysis

Our laboratory has previously reported that nitric oxide (NO)-mediated inhibition of sympathetic vasoconstriction in contracting muscle (sympatholysis) was enhanced in female, compared with male rats. Estrogen has been shown to modulate NO synthase (NOS) expression and NO-mediated sympatholysis. Therefore, this study investigated the hypothesis that NO-mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle of female rats would be a function of estrogen bioavailability. Further, exercise training has been shown to enhance sympatholysis. Thus, we also investigated the hypothesis that exercise training would restore sympatholysis in estrogen-deficient rats. Female Sprague-Dawley rats were randomized to sedentary ovary-intact (SOI, n=10), sedentary ovariectomized (SOVX, n=9), exercise-trained (10 weeks, 5 days/week, 600m, 40m·min−1, 5% grade) ovary-intact (TOI, n=13), or exercise-trained ovariectomized (TOVX, n=10) groups. OVX rats had both ovaries surgically removed. Following sedentary behavior or exercise training, rats were anesthetized and instrumented for measurement of blood pressure, femoral vascular conductance (FVC), stimulation of the lumbar sympathetic chain, and contraction of the triceps surae muscle group. The percentage change of FVC (%FVC) in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during muscle contraction (60% maximal contractile force) in control, selective neuronal NOS (nNOS) inhibition (SMTC; 0.6 mg·kg−1 IV), and non-selective NOS inhibition (L-NAME; 10 mg·kg−1 IV) conditions. In the Control condition, sympathetic vasoconstrictor responsiveness (%FVC) in resting and contracting skeletal muscle was not different between groups. Under resting conditions, sympathetic vasoconstrictor responsiveness was not different following selective nNOS inhibition (p>0.05), but was increased (p<0.05, main effect of drug) following non-selective NOS inhibition compared with control and selective nNOS inhibition conditions at both 2 Hz and 5 Hz. During muscle contraction, sympathetic vasoconstrictor responsiveness to 2 Hz sympathetic stimulation was unchanged (p>0.05) in the presence of selective nNOS inhibition, but was increased (p<0.05, main effect of drug) following non-selective NOS inhibition compared with control and selective nNOS inhibition conditions. At 5 Hz, sympathetic vasoconstrictor responsiveness was increased (p<0.05, main effect of drug) by selective nNOS inhibition, and increased further (p<0.05, main effect of drug) by non-selective NOS inhibition. The magnitude of sympatholysis at 2 Hz was not different (p>0.05) between groups or drug conditions. At 5 Hz, sympatholysis was blunted (p<0.05, main effect of drug) in the selective nNOS inhibition condition, and further reduced (p<0.05, main effect of drug condition) following non-selective NOS inhibition in all groups. Sympatholysis was not different (p>0.05) between sedentary and exercise trained groups. In conclusion: 1) sympathetic vasoconstrictor responsiveness in resting and contracting skeletal muscle was not dependent on estrogen bioavailability; 2) NO blunted vasoconstriction in all groups, however, NO-mediated sympatholysis was not altered by estrogen status, and; 3) exercise training did not alter sympathetic vasoconstrictor responsiveness or sympatholysis regardless of estrogen bioavailability. NSERC, Canada, Canadian Foundation for Innovation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Neural control of the circulation during exercise in heart failure with reduced and preserved ejection fraction.

Patients with heart failure with reduced (HFrEF) and preserved ejection fraction (HFpEF) exhibit severe exercise intolerance that may be due, in part, to inappropriate cardiovascular and hemodynamic adjustments to exercise. Several neural mechanisms and locally released vasoactive substances work in concert through complex interactions to ensure proper adjustments to meet the metabolic demands of the contracting skeletal muscle. Specifically, accumulating evidence suggests that disease-related alterations in neural mechanisms (e.g., central command, exercise pressor reflex, arterial baroreflex, and cardiopulmonary baroreflex) contribute to heightened sympathetic activation and impaired ability to attenuate sympathetic vasoconstrictor responsiveness that may contribute to reduced skeletal muscle blood flow and severe exercise intolerance in patients with HFrEF. In contrast, little is known regarding these important aspects of physiology in patients with HFpEF, though emerging data reveal heightened sympathetic activation and attenuated skeletal muscle blood flow during exercise in this patient population that may be attributable to dysregulated neural control of the circulation. The overall goal of this review is to provide a brief overview of the current understanding of disease-related alterations in the integrative neural cardiovascular responses to exercise in both HFrEF and HFpEF phenotypes, with a focus on sympathetic nervous system regulation during exercise.

Sympathetic pressor responses to glutamate nanoinjections in the rostral ventrolateral medulla are influenced by ovarian hormones in active but not sedentary female rats

Cardiovascular disease (CVD) is the leading cause of death worldwide. One of the leading risk factors for CVD is hypertension. The incidence of hypertension in females increases drastically after the onset of menopause, suggesting female reproductive hormones have cardioprotective effects. However, the interaction between female reproductive hormones and blood pressure-lowering effects of regular physical activity are poorly understood. Blood pressure is controlled by a region of the brainstem known as the rostral ventrolateral medulla (RVLM). Previously, we reported that female rats had lower resting blood pressure than male rats, but had higher sympathoexcitatory responses to direct activation of the RVLM, as did sedentary animals from both sexes. Therefore, the purpose of our study was to examine the interaction between ovarian hormones and sedentary and active conditions. We hypothesized that during low or high hormone stages, sedentary female rats would have higher blood pressure responses to activation of the RVLM compared to the physically active female rats. In addition, we hypothesized that ovariectomy (OVX) would reduce the ability of exercise to blunt pressor responses to RVLM activation. OVX or sham surgeries were performed at four weeks of age and groups were split into active (running wheels) or sedentary conditions (no running wheels) for 12 weeks. At 16 weeks of age, vaginal lavages were collected under Isoflurane anesthesia to categorize stages of the estrous cycle and all rats received glutamate nanoinjections (1, 10, & 100 mM; 30 nl ea.) into the RVLM, under Inactin anesthesia. Sedentary versus active conditions promoted significantly greater pressor responses to nanoinjections of glutamate (100 mM) in the RVLM in both the high hormone (proestrus/estrus; 25±2 vs 14±3 mmHg, p<0.001) and low hormone (diestrus/metestrus; 21±2 vs 14±2 mmHg, p=0.007) groups. In OVX rats, the beneficial effects of exercise appeared to be lost as pressor responses to 100 mM of glutamate were similar in sedentary versus active rats (20±2 vs 25±6 mmHg, resp., p>0.05). Our results indicate that the absence of ovarian hormones offset the decreased pressor responses originating from the RVLM in active but not sedentary animals and could help explain the increased risk for CVD in females after menopause. They also demonstrate the increased risks of CVD and hypertension associated with a sedentary lifestyle as a result of this greater sensitivity to sympathoexcitation. 1R01-HL161233 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The peripheral vascular responses in non-freezing cold injury and matched controls.

What is the central question of this study? Does non-freezing cold injury (NFCI) alter normal peripheral vascular function? What is the main finding and its importance? Individuals with NFCI were more cold sensitive (rewarmed more slowly and felt more discomfort) than controls. Vascular tests indicated that extremity endothelial function was preserved with NFCI and that sympathetic vasoconstrictor response might be reduced. The pathophysiology underpinning the cold sensitivity associated with NFCI thus remains to be identified. The impact of non-freezing cold injury (NFCI) on peripheral vascular function was investigated. Individuals with NFCI (NFCI group) and closely matched controls with either similar (COLD group) or limited (CON group) previous cold exposure were compared (n=16). Peripheral cutaneous vascular responses to deep inspiration (DI), occlusion (PORH), local cutaneous heating (LH) and iontophoresis of acetylcholine and sodium nitroprusside were investigated. The responses to a cold sensitivity test (CST) involving immersion of a foot in 15°C water for 2min followed by spontaneous rewarming, and a foot cooling protocol (footplate cooled from 34°C to 15°C), were also examined. The vasoconstrictor response to DI was lower in NFCI compared to CON (toe: 73 (28)% vs. 91 (17)%; P=0.003). The responses to PORH, LH and iontophoresis were not reduced compared to either COLD or CON. During the CST, toe skin temperature rewarmed more slowly in NFCI than COLD or CON (10min: 27.4 (2.3)°C vs. 30.7 (3.7)°C and 31.7 (3.9)°C, P<0.05, respectively); however, no differences were observed during the footplate cooling. NFCI were more cold-intolerant (P<0.0001) and reported colder and more uncomfortable feet during the CST and footplate cooling than COLD and CON (P<0.05). NFCI showed a decreased sensitivity to sympathetic vasoconstrictor activation than CON and greater cold sensitivity (CST) compared to COLD and CON. None of the other vascular function tests indicated endothelial dysfunction. However, NFCI perceived their extremities to be colder and more uncomfortable/painful than the controls.

Circadian Variations in Sympathetic Vasoconstriction in Older Adults with and Without Type 2 Diabetes

An impact of the sympathetic nervous system in the higher rate of cardiovascular events in the early morning compared to the evening has been claimed. Augmented sympathetic vasoconstriction increases cardiovascular risk by augmenting pulse pressure and cardiac afterload. Type 2 diabetes (T2DM) further increases sympathetic neurovascular transduction and cardiovascular risk. We assessed whether peripheral vasoconstriction triggered by a standardized sympathetic stressor is augmented at 6am vs 9pm in adults between 50-80 years with type 2 diabetes (T2DM50-80) vs healthy ones (H50-80). Mean values of sympathetic vasoconstrictor responsiveness (SVR), vascular conductance (VC), brachial artery blood flow, and mean arterial pressure were measured on the contralateral forearm over two 5-minute bouts of rest and handgrip-mediated sympathetic stimulation, respectively. Although baseline VC values were lower (p < 0.01) in the morning vs evening in both groups, SVR values in response to sympathoexcitation were similar in H50-80 (-0.43±12.44 vs -2.57±11.63 %, p = 0.73) and T2DM50-80 (+6.64±10.67 vs +5.21±7.64 %, p=0.90), but higher (p<0.01) in T2DM50-80 vs H50-80 at both day hours. Individuals with T2DM reported positive SVR values and VC change-scores, while healthy individuals reported statistically different (p< 0.02) negative SVR values and VC change-scores. Peripheral vasoconstriction triggered by a standardized sympathetic stressor is similar between morning and evening, regardless of T2DM and different baseline VC values. However, peripheral vasoconstriction responsiveness is blunted in individuals with T2DM as handgrip-mediated sympathoexcitation induces vasodilation in the contralateral forearm in adults with T2DM and vasoconstriction in healthy age-matched controls, highlighting a neurovascular response altered by T2DM.

Attenuation of pressor response to laryngoscopy and intubation with topical lignocaine 10% spray in the controlled hypertensive patients

Laryngoscopy and tracheal intubation is invariably associated with a reflex sympathetic pressor response resulting in elevated heart rate and blood pressure. There are many studies conducted to attenuate this pressor response, the present study is undertaken to compare efficacy of 10% lignocaine spray with normal saline spray applied before induction in attenuating the pressor response to laryngoscopy and intubation in controlled hypertensive patients. Methods: 60 patients of either sex aged between35-60 years, belonging to ASA I and II undergoing elective surgery requiring general anaesthesia with endotracheal intubation were included. Patients were randomly divided in two groups of 30 patients each. Group I (Study group) received topical lignocaine 10% spray 2 minutes before intravenous induction. Group II (Control group) received topical normal saline 2 minutes before intravenous induction. Results: Showed that the topical lignocaine 10% spray significantly attenuates the rise in mean systolic blood pressure, diastolic blood pressure and heart rate when compared with the baseline as well as the control group. There was a statistically significant (p<0.05) increase in heart rate, systolic and diastolic blood pressure in group II when compared to group I and baseline values. Conclusion: Study concluded that topical lignocaine 10% spray did not completely abolish the rise in heart rate, SBP and DBP but only attenuate it when compared with the baseline or control group.

Comparison of non-invasive haemodynamic monitors of stress response to endo-tracheal intubation with perfusion index in patients undergoing elective surgery

Introduction: Laryngoscopy and intubation is always associated with a short term reflex sympathetic pressor response. The perfusion index is an indirect, non-invasive, and continuous measure of peripheral perfusion by pulse oximeter which can detect the stress response to intubation similar to heart rate, systolic blood pressure and diastolic blood pressure.&#x0D; Methods: This prospective observational study enrolled sixty-five normotensive patients of American society of anesthesiologists physical status grade I and II scheduled for elective surgery under general anaesthesia. Tracheal intubation was performed after induction with intravenous fentanyl, propofol and vecuronium. Heart rate, Systolic and Diastolic Blood Pressure and Perfusion Index were measured before induction of anesthesia, before intubation and one minute, three minutes, five minutes after the insertion of the endotracheal tube. Increase in heart rate by ?10 beats per minute, systolic and diastolic blood pressure by ?15 millimeters of mercury and decrease in Perfusion index ?10% after endotracheal intubation as compared to preintubationvalue were considered positive haemodynamic changes.&#x0D; Results: Endotracheal intubation produced a significant increase in heart rate and blood pressure whereas perfusion index decreased significantly. Our study showed that perfusion index response criterion achieved 97.7% (Confidence interval 97.58-97.86) sensitivity in detecting the stress response to insertion of endotracheal tube whereas systolic and diastolic blood pressure achieved sensitivity of 90% and 92% respectively.&#x0D; Conclusion: Perfusion Index is easier, reliable and non-invasive alternative to conventional haemodynamic criteria for detection of stress response to endotracheal intubation.

Attenuation of sympathetic pressor responses to laryngoscopy and intubation in patients with preeclampsia: Comparison between IV lignocaine and IV lignocaine with labetalol

Attenuation of sympathetic pressor responses to laryngoscopy and intubation in patients with preeclampsia: Comparison between IV lignocaine and IV lignocaine with labetalol - IJCA- Print ISSN No: - 2394-4781 Online ISSN No:- 2394-4994 Article DOI No:- 10.18231/2394-4994.2018.0011, Indian Journal of Clinical Anaesthesia

The Effect Of A High-fat Meal On Sympathetic Vasoconstrictor Responsiveness In Men And Women

Consumption of a high-fat (HF) meal has been shown to reduce flow-mediated dilation (FMD) in men, but not women. This decline in FMD may be a result of decreased nitric oxide (NO) bioavailability. NO inhibits sympathetic vasoconstriction and a HF meal may, therefore, heighten sympathetic vasoconstrictor responsiveness. However, the effect of a HF meal on sympathetic vasoconstriction in men and women has not been investigated. PURPOSE: The purpose of this study was to investigate the hypothesis that consumption of a HF meal would heighten sympathetic vasoconstrictor responsiveness in men, but have no effect in women. METHODS: In a randomized cross-over design, young males (n=15) and females (n=15) consumed a HF or an isocaloric low-fat (LF) meal on separate days. Two hours post-meal, subjects underwent a cold pressor test (CPT) and measurement of brachial artery FMD to determine sympathetic vasoconstrictor responsiveness and endothelial function, respectively. Beat-by-beat blood pressure was measured by Finometer and mean arterial pressure (MAP) was calculated. Forearm blood flow (FBF) was measured by Doppler ultrasound at the brachial artery and forearm vascular conductance (FVC) was calculated as FBF/MAP. Sympathetic vasoconstrictor responsiveness was calculated as the percentage decrease in FVC (%∆FVC) in response to CPT. FMD was calculated as the percentage increase in brachial artery diameter from baseline and normalized for cumulative shear rate. RESULTS: Sympathetic vasoconstrictor responsiveness was not different (p>0.05) between meal conditions or between females (LF: -27±14%: HF: -30±15%) and males (LF: -29±23%: HF: -24±16%) in either meal condition. FMD was higher (main effect of sex; p<0.05) in females (LF: 8.1±2.1%: HF: 7.4±1.4%) compared to males (LF: 6.2±1.5%: HF: 5.1±1.1%) and FMD was lower (main effect of meal; p<0.05) in the HF compared to the LF meal condition. No interaction (p>0.05) was observed between meal condition and sex for FMD. FMD normalized for shear rate was not different (p>0.05) between meal conditions or between females and males in either meal condition. CONCLUSION: These data suggest that, despite evidence of a post-prandial decrease in endothelial function, a HF meal does not alter sympathetic vasoconstrictor responsiveness in men or women.

Effect of acute dietary nitrate supplementation on sympathetic vasoconstriction at rest and during exercise.

Dietary nitrate ( ) supplementation has been shown to reduce resting blood pressure. However, the mechanism responsible for the reduction in blood pressure has not been identified. Dietary supplementation may increase nitric oxide (NO) bioavailability, and NO has been shown to inhibit sympathetic vasoconstriction in resting and contracting skeletal muscle. Therefore, the purpose of this study was to investigate the hypothesis that acute dietary supplementation would attenuate sympathetic vasoconstrictor responsiveness at rest and during exercise. In a double-blind randomized crossover design, 12 men (23 ± 5 yr) performed a cold-pressor test (CPT) at rest and during moderate- and heavy-intensity alternate-leg knee-extension exercise after consumption of rich beetroot juice (~12.9 mmol ) or a -depleted placebo (~0.13 mmol ). Venous blood was sampled before and 2.5 h after the consumption of beetroot juice for the measurement of total plasma nitrite/ [NOx]. Beat-by-beat blood pressure was measured by Finometer. Leg blood flow was measured at the femoral artery via Doppler ultrasound, and leg vascular conductance (LVC) was calculated. Sympathetic vasoconstrictor responsiveness was calculated as the percentage decrease in LVC in response to the CPT. Total plasma [NOx] was greater (P < 0.001) in the (285 ± 120 µM) compared with the placebo (65 ± 30 µM) condition. However, mean arterial blood pressure and plasma catecholamines were not different (P > 0.05) between and placebo conditions at rest or during moderate- and heavy-intensity exercise. Sympathetic vasoconstrictor responsiveness (Δ% LVC) was not different (P > 0.05) between and placebo conditions at rest ( : -33 ± 10%; placebo: -35 ± 11%) or during moderate ( : -18 ± 8%; placebo: -20 ± 10%)- and heavy ( : -12 ± 8%; placebo: -11 ± 9%)-intensity exercise. These data demonstrate that acute dietary supplementation does not alter sympathetic vasoconstrictor responsiveness at rest or during exercise in young healthy males. NEW & NOTEWORTHY Dietary nitrate may increase nitric oxide bioavailability, and nitric oxide has been shown to attenuate sympathetic vasoconstriction in resting and contracting skeletal muscle and enhance functional sympatholysis. However, the effect of dietary nitrate on sympathetic vasoconstrictor responsiveness is unknown. Acute dietary nitrate supplementation did not alter blood pressure or sympathetic vasoconstrictor responsiveness at rest or during exercise in young healthy males.

β-Adrenoreceptors do not oppose sympathetic vasoconstriction in resting and contracting skeletal muscle of male rats.

Sympathetic nervous system (SNS) vasoconstriction is primarily achieved through the binding of norepinephrine (NE) to α-adrenoreceptors. However, NE may also bind to β-adrenoreceptors and cause vasodilation that may oppose/blunt SNS-mediated vasoconstriction. Therefore, this study investigated the hypothesis that β-adrenoreceptor-mediated vasodilation opposes evoked vasoconstriction in resting and contracting skeletal muscle. Male (n = 9) Sprague-Dawley rats were anesthetized and surgically instrumented for stimulation of the lumbar sympathetic chain and measurement of arterial blood pressure and femoral artery blood flow. The percentage change of femoral vascular conductance in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during triceps surae skeletal muscle contraction before (control) and after β-adrenoreceptor blockade (propranolol; 0.075 mg·kg-1, intravenously). β-Adrenoreceptor blockade did not alter (P > 0.05) baseline hemodynamics or the hyperemic response to exercise. At the 2 Hz stimulation frequency, sympathetic vasoconstriction was similar (P > 0.05) in control and β-blockade conditions in resting (control, -34% ± 6%; β-blockade, -33% ± 8%) and contracting (control, -16% ± 6%; β-blockade, -14% ± 7%) muscle. At the 5 Hz stimulation frequency, sympathetic vasoconstrictor responsiveness was reduced (main effect of drug, P < 0.05) following β-blockade (rest: control, -52% ± 7%; β-blockade, -51% ± 9%; contraction: control, -32% ± 11%; β-blockade, -29% ± 13%). Novelty These data indicate that β-adrenoreceptor blockade did not augment sympathetic vasoconstriction at rest or during exercise. The study demonstrates that β-adrenoreceptors do not oppose evoked sympathetic vasoconstriction in resting or contracting skeletal muscle or contribute to functional sympatholysis.

The Effect of Beta‐Adrenergic Receptor Blockade on Sympathetic Vasoconstrictor Responsiveness in Sedentary and Exercise‐Trained Female Rats

Stimulation of the sympathetic nervous system evokes the release of neurotransmitters and produces vasoconstriction that is primarily mediated by the binding of norepinephrine (NE) to alpha‐adrenergic receptors. However, NE may also bind to beta‐ adrenergic receptors and produce vasodilation that opposes vasoconstriction. Therefore, in the present study, we tested the hypothesis that beta‐adrenergic receptor blockade would augment sympathetic vasoconstrictor responsiveness in resting and contracting skeletal muscle of sedentary and exercise trained female rats, demonstrating beta‐adrenergic receptor mediated opposition of vasoconstriction. We also hypothesized that the increase in sympathetic vasoconstrictor responsiveness in the presence of beta‐adrenergic blockade would be larger in exercise‐trained rats, indicating that exercise training augments beta‐adrenergic receptor mediated opposition of vasoconstriction. Female Sprague‐Dawley rats were randomized to Sedentary (n=8, 265 ± 28 g) and Exercise Trained (n=9, 290 ± 27 g) groups. Exercise Trained rats completed a 4‐week treadmill training regimen (5 d/week, 15 min at 40 m/min, 5% gradient). Subsequently, rats were anaesthetized and instrumented for the measurement of femoral vascular conductance (FVC), stimulation of the lumbar sympathetic chain, and contraction of the triceps surae muscle group. The percentage change of femoral vascular conductance (Δ%FVC) in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during triceps surae muscle contraction (60% maximal contractile force) before (Control) and after beta‐adrenergic blockade (Propranolol; 0.075 mg/kg body mass, I.V.). Sympathetic vasoconstrictor responsiveness (Δ%FVC) was not different (P &gt; 0.05) between Sedentary and Exercise Trained rats at rest or during contraction. At rest, beta‐adrenergic receptor blockade did not increase (P &gt; 0.05) sympathetic vasoconstrictor responsiveness in Sedentary (Control: 2Hz: −34 ± 9 %, 5Hz: −53 ± 8 %; Propranolol: 2Hz: −31 ± 10 %, 5Hz: −49 ± 8 %) or Exercise Trained (Control: 2Hz: −38 ± 9 %, 5Hz: −57 ± 8 %; Propranolol: 2Hz: −34 ± 7 %, 5Hz: −53 ± 8 %) rats. Similarly, beta‐adrenergic receptor blockade did not increase (P &gt; 0.05) sympathetic vasoconstrictor responsiveness during exercise in Sedentary (Control: 2Hz: −7 ± 4 %, 5Hz: −20 ± 11 %; Propranolol: 2Hz: −6 ± 5 %, 5Hz: −18 ± 10 %) or Exercise Trained (Control: 2Hz: −10 ± 8 %, 5Hz: −28 ± 8 %; Propranolol: 2Hz: −6 ± 5 %, 5Hz: −24 ± 12 %) rats. In conclusion, beta‐adrenergic receptor blockade did not augment sympathetic vasoconstrictor responsiveness in resting or contracting skeletal muscle of sedentary or exercise‐trained female rats, suggesting that beta‐adrenergic receptor mediated vasodilation did not oppose vasoconstriction, regardless of training status.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada, Canadian Foundation for Innovation, and Alberta Advanced Education and Technology.This 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 Exercise Training on Sympathetic Vasoconstrictor Responsiveness and Sympatholysis in Female Rats

Our laboratory has previously reported that aerobic exercise training enhances contraction‐mediated inhibition of sympathetic vasoconstriction (sympatholysis) in male rats. Whether aerobic exercise training has a similar effect in female rats has not been established. Therefore, the purpose of the present study was to investigate the hypothesis that aerobic exercise training would blunt sympathetic vasoconstrictor responsiveness and enhance sympatholysis in female rats. Female Sprague‐Dawley rats were randomly assigned to sedentary (n=10) or treadmill exercise training (n=8) groups (15 min at 40 m/min, 5% gradient; 5 d/week) for 10 weeks. Following the completion of the sedentary behavior or exercise training intervention, rats were anaesthetized and instrumented for stimulation of the lumbar sympathetic chain and the measurement of arterial blood pressure and femoral vascular conductance (FVC). The triceps surae muscle group was stimulated to contract rhythmically at 60% of maximal contractile force. The percentage change of FVC (Δ%FVC) in response to sympathetic stimulation delivered at 2 and 5 Hz was determined at rest and during contraction. At rest, sympathetic vasoconstrictor responsiveness (Δ%FVC) was not different (p&gt;0.05) between sedentary and exercise trained rats in response to sympathetic stimulation delivered at 2Hz (Sedentary: −39 ± 12 %; Exercise Trained: −45 ± 9 %) and 5Hz (Sedentary: −57 ± 8 %; Exercise Trained: −61 ± 9 %). Muscle contraction blunted (p&lt;0.05) sympathetic vasoconstrictor responsiveness in both sedentary and exercise trained rats and the magnitude of sympatholysis was not different (p&gt;0.05) between sedentary (2Hz: 24 ± 8 %; 5Hz: 29 ± 10 %) and exercise‐trained (2Hz: 30 ± 10 %; 5Hz: 29 ± 13 %) rats. These data demonstrate that aerobic exercise training does not alter sympathetic vasoconstrictor responsiveness or contraction mediated inhibition of sympathetic vasoconstriction (sympatholysis) in female rats. Further investigation is required to determine why female rats respond differently to exercise training than male rats.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada, Canadian Foundation for Innovation, and Alberta Advanced Education and Technology.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Absence Of Sympathetic Vasodilation During Mental Stress With Non‐Dipping Circadian Blood Pressure Pattern In Young White And Black Adults Could Be An Early Indicator Of Hypertension

People of Black African ethnicity (BA) have greater prevalence of hypertension compared with those of White European ethnicity (WE) and are at greater risk of developing hypertension‐associated cardiovascular disease (CVD). Older WE non‐dipper hypertensives show endothelial dysfunction. Endothelial dysfunction and higher prevalence of non‐dipping nocturnal blood pressure have been documented in Blacks relative to Whites. Novel environmental stress stimuli evoke sympathetic vasoconstriction in renal and splanchnic vasculature, but vasodilatation in limb muscle, which may habituate on repetition. In young adults altered response to novel stimuli is predictive of developing hypertension later on in life. However, It is not known whether non‐dippers also show endothelial dysfunction and altered responses to environmental stressors. Thus, we hypothesized that non dippers would show smaller muscle vasodilator or muscle vasoconstrictive responses on repetition of an environmental stressor and blunted reactive hyperaemia relative to dippers. Experiments were performed on 17 WEs (21±0.64 years) and 16 BAs (22±0.77 years) who were resident in the UK. Responses were recorded following release of arterial occlusion for 2 min (reactive hyperaemia) and by 5 sound stimuli (S1–5; 100 dB, 2 KHz). Continuous arterial blood pressure (ABP) was recorded by finger photoplethysmography. Forearm blood flow (FBF) was recorded by venous occlusion plethysmography; forearm vascular conductance (FVC) was calculated as FBF/ABP. 24 hour Ambulatory blood pressure monitoring was done. Relative to WES, BAs showed higher 24 hour systolic blood pressure (SBP)(110±1.33 vs 117±3.17 mmHg) and higher sleep‐time SBP (99±1.36 vs 108±3.05 mmHg) p&lt;0.05 as well as higher proportion of pre‐/hypertensives (7/16, 40%) compared with WE (1,5.8%). 40% BAs were non‐ dippers compared to 17.6 % WE. Six of the pre‐/hypertensive BAs were nocturnal dippers. Relative to normotensive BA dippers, BA non‐dippers showed higher sleep SBP (93±4.65 vs 108±3.01 mmHg) and heart rate (59±4.69 vs 72±3.11 bpm) p&lt;0.05. Relative to WE dippers, the WE non dippers showed higher day‐time and night time mean ABP (85.25±1.14 vs 91.57±2.39 mmHg) ; (71.55±0.88 vs 81.25±1.71 mmHg) p&lt;0.05. During reactive hyperaemia, there was no difference between dippers and non‐dippers in the two ethnic groups ( WE: +0.39± 0.03 vs +0.45± 0.08; BA : +0.41± 0.05 vs +0.34± 0.05 p&gt;0.05 ). During S1–5, WE and BA dippers showed a net increase in FVC indicating forearm vasodilatation (WE, +0.005±0.002 CU; BA, +0.007±0.002 CU) whilst WE and BA non‐dippers showed a net decrease in FVC indicating forearm vasoconstriction, (WE − 0.007±0.004 CU; BA −0.007±0.003 CU). These results indicate that in young normotensive non‐dippers, sympathetic vasoconstriction to mental stress precedes development of endothelial dysfunction and could serve as an early indicator of cardiovascular disorder. Thus, we propose that exaggerated sympathetic vasoconstrictor response to environmental stressors contributes to the development of hypertension and CVD in non‐dippersThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Sex differences in sympathetic vasoconstrictor responsiveness and sympatholysis

Sex differences in the neurovascular control of blood pressure and vascular resistance have been reported. However, the mechanisms underlying the modulatory influence of sex have not been fully elucidated. Nitric oxide (NO) has been shown to inhibit sympathetic vasoconstriction in resting and contracting skeletal muscle, and estrogen modulates NO synthase (NOS) expression and NO bioavailability. Therefore NO-mediated inhibition of sympathetic vasoconstriction may be enhanced in females. Thus the purpose of the present study was to investigate the hypothesis that sympathetic vasoconstrictor responsiveness would be blunted and NO-mediated inhibition of sympathetic vasoconstriction would be enhanced in females compared with males. Male (M; n = 8) and female (F; n = 10) Sprague-Dawley rats were anesthetized and surgically instrumented for measurement of arterial blood pressure and femoral artery blood flow and stimulation of the lumbar sympathetic chain. The percentage change of femoral vascular conductance in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during triceps surae muscle contraction before (control) and after NOS blockade [Nω-nitro-l-arginine methyl ester (l-NAME), 10 mg/kg iv]. At rest, sympathetic vasoconstrictor responsiveness was augmented (P < 0.05) in female compared with male rats at 2 Hz [F: -33 ± 8% (SD); M: -26 ± 6%] but was not different at 5 Hz (F: -55 ± 7%; M: -47 ± 7%). During muscle contraction, evoked vasoconstriction was similar (P > 0.05) in females and males at 2 Hz (F: -12 ± 5%; M: -13 ± 5%) but was blunted (P < 0.05) in females compared with males at 5 Hz (F: -24 ± 5%; M: -34 ± 8%). l-NAME increased (P < 0.05) sympathetic vasoconstrictor responsiveness in both groups at rest and during contraction. Contraction-mediated inhibition of vasoconstriction (sympatholysis) was enhanced (P < 0.05) in females compared with males; however, sympatholysis was not different (P > 0.05) between males and females in the presence of NOS blockade, indicating that NO-mediated sympatholysis was augmented in female rats. These data suggest that sex modulates sympathetic vascular control in resting and contracting skeletal muscle and that a portion of the enhanced sympatholysis in female rats was NO dependent.NEW & NOTEWORTHY Sex differences in the neurovascular regulation of blood pressure and vascular resistance have been documented. However, our understanding of the underlying mechanisms that mediate these differences is incomplete. The present study demonstrates that female rats have an enhanced capacity to inhibit sympathetic vasoconstriction during exercise (sympatholysis) and that NO mediates a portion of the enhanced sympatholysis.

Sex Differences in Sympathetic Vasoconstrictor Responsiveness and Sympatholysis

Sympathetic nervous system control of blood pressure and skeletal muscle vascular resistance appears to differ between males and females. The mechanism(s) responsible for sex differences in neurovascular control have not been fully elucidated. Nitric Oxide (NO) has been shown to inhibit sympathetic vasoconstriction in resting and contracting skeletal muscle and estrogen appears to modulate NO synthase (NOS) expression and NO bioavailability. The relative abundance of estrogen in females compared to males suggests that NO‐mediated inhibition of sympathetic vasoconstriction may be augmented in females relative to males. Therefore, the purpose of the present study was to investigate the hypothesis that compared to males, females would have blunted sympathetic vasoconstrictor responsiveness and augmented NO‐mediated inhibition of sympathetic vasoconstriction at rest and during exercise. Male (n=8) and Female (n=10) Sprague‐Dawley rats were anesthetized and surgically instrumented for measurement of arterial blood pressure and femoral artery vascular conductance (FVC) and stimulation of the lumbar sympathetic chain. The percentage change of FVC (%FVC) in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during triceps surae muscle contraction before (control) and after NOS‐blockade (L‐NAME; 10 mg·kg−1 IV). At rest, vasoconstrictor responsiveness to sympathetic stimulation delivered at 2Hz was augmented (p&lt;0.05) in females (−33 ± 8%) compared to males (−26 ± 6%), whereas vasoconstrictor responsiveness to sympathetic stimulation delivered at 5Hz was not different (p&gt;0.05) between females (−55 ± 7%) and males (−47 ± 7%). Muscle contraction blunted (p&lt;0.05) sympathetic vasoconstrictor responsiveness in both female and male rats; however the magnitude of sympatholysis was greater (p&lt;0.05) in female (2Hz: 22 ± 8%; 5Hz: 30 ± 7%) compared to male (2Hz: 12 ± 6%; 5Hz: 13 ± 8%) rats. NOS blockade did not alter (p&gt;0.05) sympatholysis of responses evoked at 2Hz in females or males; however L‐NAME reduced (p&lt;0.05) sympatholysis of responses evoked at 5Hz in female rats. These data demonstrate that resting sympathetic vasoconstrictor responsiveness was augmented in female rats compared to male rats in a stimulation frequency‐dependent manner. Furthermore, sympatholysis was enhanced in female compared to male rats and this was partly attributable to augmented NO‐mediated inhibition of sympathetic vasoconstriction.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada (NSERC), Canadian Foundation for Innovation, and Alberta Advanced Education and Technology.

Sympathetic vasoconstrictor response to lower body negative pressure in young obese adults: the preliminary finding

Sympathetic vasoconstrictor response to lower body negative pressure in young obese adults: the preliminary finding

Sympathetic Vasoconstriction in Skeletal Muscle: Adaptations to Exercise Training.

Sympathetic vasoconstriction in the skeletal muscle vascular bed is essential for the regulation of vascular resistance and therefore control of blood pressure and muscle blood flow at rest and during exercise. In this article, we address the hypothesis that aerobic exercise training alters sympathetic vasoconstrictor responsiveness and enhances contraction-mediated inhibition of sympathetic vasoconstriction (functional sympatholysis) through a nitric oxide–dependent mechanism.

Sympathetic Neural and Hemodynamic Responses to Painful Stimuli are Related to Perception of Pain

Painful stimuli cause activation of the sympathetic nervous system, increasing efferent muscle sympathetic nerve activity (MSNA) and altering downstream hemodynamic responses. However, there is considerable inter-individual variability in the perception of pain to a given painful stimulus; how this magnitude of perceived pain relates to sympathetic neural and hemodynamic responses remains to be fully elucidated. PURPOSE: Thus, the purpose of this study was to evaluate the relationship between the perception of pain and the corresponding sympathetic neural and hemodynamic responses to a painful stimulus in healthy normotensive men and women. METHODS: Heart rate (HR), MSNA, and blood pressure (BP) were measured at baseline (supine, rest) and during a two-minute cold pressor test (CPT) in 15 subjects (6 female, 9 male; age: 31.5 ± 7.5 years, body mass index (BMI): 25.1 ± 3.4 kg/m2, mean ± SD). Stroke volume (SV), cardiac output (Qc), and total peripheral resistance (TPR) were calculated using the model flow method. Immediately following the CPT subjects rated their pain on a verbal descriptor scale (Numerical Rating Scale, range 0-10). Statistical significance was set at p < 0.05. RESULTS: Subjects were grouped according to pain ratings given following the CPT (Pain ≥7, i.e., “severe” pain, n=9; and Pain ≤ 6, i.e. “none” to “mild-to-moderate” pain, n=6). The two groups were similar with regards to gender, age, and BMI. Subjects who rated their Pain >6 had significantly larger increases during the CPT in MSNA total activity (1208 ± 631 vs. 173 ± 87 a.u./min), burst frequency (24 ± 15 vs. 9 ± 6 bursts/min), burst incidence (38 ± 18 vs. 13 ± 5 bursts/100 heartbeats,), TPR (223 ± 178 vs.79 ± 107 dynes/s/cm-5), Qc (1.26 ± 0.63 vs. 0.54 ± 0.39 L/min) and mean BP (15 ± 6 vs. 6 ± 7 mmHg) compared to individuals who rated their Pain ≤6 (n=6). Changes in HR and SV in response to the CPT were not related to pain ratings. CONCLUSION: In healthy, normotensive men and women, the sympathetic neural, BP, & vasoconstrictor responses to a fixed painful stimulus are positively related to the magnitude of pain perception. These findings may have important clinical implications, as hypoalgesia (i.e., decreased sensitivity to pain) is a common characteristic of many cardiovascular disease states.

Acute Dietary Nitrate Supplementation Does Not Alter Sympathetic Vasoconstrictor Responsiveness At Rest And During Exercise.

Acute Dietary Nitrate Supplementation Does Not Alter Sympathetic Vasoconstrictor Responsiveness At Rest And During Exercise.