Thermogenic responsiveness to nonspecific β-adrenergic stimulation is not related to genetic variation in codon 16 of the β2-adrenergic receptor

2006 ◽  
Vol 290 (4) ◽  
pp. E703-E707 ◽  
Author(s):  
Christopher Bell ◽  
Nicole R. Stob ◽  
Douglas R. Seals
Keyword(s):  
Genetic Variation ◽  
Muscle Sympathetic Nerve Activity ◽  
Fat Free Mass ◽  
Group Differences ◽  
Plasma Norepinephrine ◽  
Adrenergic Stimulation ◽  
Healthy Humans ◽  
Β2 Adrenergic Receptor ◽  
Β Adrenergic Receptors ◽  
Thermogenic Response

Stimulation of β-adrenergic receptors (β-AR) by the sympathetic nervous system (SNS) modulates energy expenditure (EE), but substantial interindividual variability is observed. We determined whether the thermogenic response to β-AR stimulation is related to genetic variation in codon 16 of the β2-AR, a biologically important β-AR polymorphism, and whether differences in SNS activity (i.e., the stimulus for agonist-promoted downregulation) are involved. The increase in EE (ΔEE, indirect calorimetry, ventilated hood) above resting EE in response to nonspecific β-AR stimulation [iv isoproterenol: 6, 12, and 24 ng/kg fat-free mass (FFM)/min] was measured in 46 healthy adult humans [Arg16Arg: 9 male, 7 female, 48 ± 5 yr; Arg16Gly: 11 male, 4 female, 53 ± 5 yr; Gly16Gly: 3 male, 12 female, 48 ± 5 yr (means ± SE)]. Neither FFM-adjusted baseline resting EE ( P = 0.83) nor the dose of isoproterenol required to increase EE 10% above resting ( P = 0.87) differed among the three groups (Arg16Arg: 5,409 ± 209 kJ/day, 11.2 ± 2.1 ng·kg FFM−1·min−1; Arg16Gly: 5,367 ± 272 kJ/day, 11.1 ± 2.1 ng·kg FFM−1·min−1; Gly16Gly: 5,305 ± 159 kJ/day, 10.5 ± 1.4 ng·kg FFM−1·min−1). Consistent with this, muscle sympathetic nerve activity and plasma norepinephrine concentrations were not different among the groups. Group differences in sex composition did not influence the results. Our findings indicate that the thermogenic response to nonspecific β-AR stimulation, an important mechanistic component of overall β-AR modulation of EE, is not related to this β2-AR polymorphism in healthy humans. This may be explained in part by a lack of association between this gene variant and tonic SNS activity.

scholarly journals Short-term sympathoadrenal inhibition augments the thermogenic response to β-adrenergic receptor stimulation

2010 ◽  
Vol 206 (3) ◽  
pp. 307-315 ◽  
Author(s):  
Sean A Newsom ◽  
Jennifer C Richards ◽  
Tyler K Johnson ◽  
Jessica N Kuzma ◽  
Mark C Lonac ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Adrenergic Receptor ◽  
Muscle Sympathetic Nerve Activity ◽  
Fat Free Mass ◽  
Plasma Norepinephrine ◽  
Short Term ◽  
Norepinephrine Concentration ◽  
Sympathoadrenal Activity ◽  
Important Regulator ◽  
Thermogenic Response

Sedentary behavior is associated with an attenuated thermogenic response to β-adrenergic receptor (β-AR) stimulation, an important regulator of energy expenditure (EE) in humans. Chronic stimulation of β-ARs, via heightened activity of the sympathoadrenal system, leads to diminished β-AR function. We have investigated the hypothesis that the thermogenic response of sedentary adults to β-AR stimulation will be increased during short-term sympathoadrenal inhibition. Using a randomly ordered, repeated measures study design, resting EE (REE; indirect calorimetry, ventilated hood technique) and the % increase in EE above REE (%ΔEE) during acute i.v. isoproterenol administration (nonselective β-AR agonist; 6, 12, and 24 ng/kg fat-free mass per min) were determined in 16 sedentary adults (nine females and seven males, 25±1 years, body mass index: 26.1±0.9 kg/m2, maximal oxygen uptake: 40±2 ml/kg per min (mean±s.e.m.)) in the basal state and on the 6th day of transdermal clonidine administration (centrally acting α2-AR agonist; 0.2 mg/day). Relative to baseline, clonidine inhibited sympathoadrenal activity, as evidenced by decreased plasma norepinephrine concentration (1.04±0.13 vs 0.34±0.03 nmol/l; P<0.001), skeletal muscle sympathetic nerve activity (22.5±3.8 vs 8.5±1.9 bursts/min; P=0.003), and resting heart rate (63±2 vs 49±1 beats/min; P<0.001). Sympathoadrenal inhibition decreased REE (6510±243 vs 5857±218 kJ/day; P<0.001), increased respiratory exchange ratio (0.84±0.01 vs 0.86±0.01; P=0.03), and augmented the thermogenic response to β-AR stimulation (%ΔEE: 11±2, 16±2, and 24±2 vs 14±1, 20±2, and 31±2; P=0.04). These data demonstrate that in sedentary humans, short-term inhibition of sympathoadrenal activity increases the thermogenic response to β-AR stimulation, an important determinant of EE and hence energy balance.

scholarly journals Increased β-adrenergic stimulation augments vascular smooth muscle cell calcification via PKA/CREB signalling

2021 ◽  
Author(s):  
Barbara Moser ◽  
Florian Poetsch ◽  
Misael Estepa ◽  
Trang T. D. Luong ◽  
Burkert Pieske ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Vascular Calcification ◽  
Sympathetic Innervation ◽  
Adrenergic Stimulation ◽  
Binding Factor ◽  
Β2 Adrenergic Receptor ◽  
Factor Α ◽  
Β Adrenergic Receptors ◽  
High Phosphate

AbstractIn chronic kidney disease (CKD), hyperphosphatemia promotes medial vascular calcification, a process augmented by osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). VSMC function is regulated by sympathetic innervation, and these cells express α- and β-adrenergic receptors. The present study explored the effects of β2-adrenergic stimulation by isoproterenol on VSMC calcification. Experiments were performed in primary human aortic VSMCs treated with isoproterenol during control or high phosphate conditions. As a result, isoproterenol dose dependently up-regulated the expression of osteogenic markers core-binding factor α-1 (CBFA1) and tissue-nonspecific alkaline phosphatase (ALPL) in VSMCs. Furthermore, prolonged isoproterenol exposure augmented phosphate-induced calcification of VSMCs. Isoproterenol increased the activation of PKA and CREB, while knockdown of the PKA catalytic subunit α (PRKACA) or of CREB1 genes was able to suppress the pro-calcific effects of isoproterenol in VSMCs. β2-adrenergic receptor silencing or inhibition with the selective antagonist ICI 118,551 blocked isoproterenol-induced osteogenic signalling in VSMCs. The present observations imply a pro-calcific effect of β2-adrenergic overstimulation in VSMCs, which is mediated, at least partly, by PKA/CREB signalling. These observations may support a link between sympathetic overactivity in CKD and vascular calcification.

scholarly journals Role of the carotid chemoreceptors in insulin-mediated sympathoexcitation in humans

2020 ◽  
Vol 318 (1) ◽  
pp. R173-R181 ◽  
Author(s):  
Jacqueline K. Limberg ◽  
Blair D. Johnson ◽  
Michael T. Mozer ◽  
Walter W. Holbein ◽  
Timothy B. Curry ◽  
...  
Keyword(s):  
Sympathetic Nerve Activity ◽  
Low Dose ◽  
Muscle Sympathetic Nerve Activity ◽  
Healthy Adults ◽  
Fat Free Mass ◽  
Burst Frequency ◽  
Nerve Activity ◽  
Carotid Chemoreceptors ◽  
Healthy Humans

We examined the contribution of the carotid chemoreceptors to insulin-mediated increases in muscle sympathetic nerve activity (MSNA) in healthy humans. We hypothesized that reductions in carotid chemoreceptor activity would attenuate the sympathoexcitatory response to hyperinsulinemia. Young, healthy adults (9 male/9 female, 28 ± 1 yr, 24 ± 1 kg/m2) completed a 30-min euglycemic baseline followed by a 90-min hyperinsulinemic (1 mU·kg fat-free mass−1·min−1), euglycemic infusion. MSNA (microneurography of the peroneal nerve) was continuously measured. The role of the carotid chemoreceptors was assessed at baseline and during hyperinsulinemia via 1) acute hyperoxia, 2) low-dose dopamine (1–4 µg·kg−1·min−1), and 3) acute hyperoxia + low-dose dopamine. MSNA burst frequency increased from baseline during hyperinsulinemia ( P < 0.01). Acute hyperoxia had no effect on MSNA burst frequency at rest ( P = 0.74) or during hyperinsulinemia ( P = 0.83). The insulin-mediated increase in MSNA burst frequency ( P = 0.02) was unaffected by low-dose dopamine ( P = 0.60). When combined with low-dose dopamine, acute hyperoxia had no effect on MSNA burst frequency at rest ( P = 0.17) or during hyperinsulinemia ( P = 0.85). Carotid chemoreceptor desensitization in young, healthy men and women does not attenuate the sympathoexcitatory response to hyperinsulinemia. Our data suggest that the carotid chemoreceptors do not contribute to acute insulin-mediated increases in MSNA in young, healthy adults.

β-blockade abolishes the augmented cardiac tPA release induced by transactivation of heterodimerised bradykinin receptor-2 and β2-adrenergic receptor in vivo

2014 ◽  
Vol 112 (11) ◽  
pp. 951-959 ◽  
Author(s):  
Morten Eriksen ◽  
Arnfinn Ilebekk ◽  
Alessandro Cataliotti ◽  
Cathrine Rein Carlson ◽  
Torstein Lyberg ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Sympathetic Nerves ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Adrenergic Stimulation ◽  
Β2 Adrenergic Receptor ◽  
Β Blocker

SummaryBradykinin (BK) receptor-2 (B2R) and β2-adrenergic receptor (β2AR) have been shown to form heterodimers in vitro. However, in vivo proofs of the functional effects of B2R-β2AR heterodimerisation are missing. Both BK and adrenergic stimulation are known inducers of tPA release. Our goal was to demonstrate the existence of B2R-β2AR heterodimerisation in myocardium and to define its functional effect on cardiac release of tPA in vivo. We further investigated the effects of a non-selective β-blocker on this receptor interplay. To investigate functional effects of B2R-β2AR heterodimerisation (i. e. BK transactivation of β2AR) in vivo, we induced serial electrical stimulation of cardiac sympathetic nerves (SS) in normal pigs that underwent concomitant BK infusion. Both SS and BK alone induced increases in cardiac tPA release. Importantly, despite B2R desensitisation, simultaneous BK infusion and SS (BK+SS) was characterised by 2.3 ± 0.3-fold enhanced tPA release compared to SS alone. When β-blockade (propranolol) was introduced prior to BK+SS, tPA release was inhibited. A persistent B2R-β2AR heterodimer was confirmed in BK-stimulated and nonstimulated left ventricular myocardium by immunoprecipitation studies and under non-reducing gel conditions. All together, these results strongly suggest BK transactivation of β2AR leading to enhanced β2AR-mediated release of tPA. Importantly, non-selective β-blockade inhibits both SS-induced release of tPA and the functional effects of B2R-β2AR heterodimerisation in vivo, which may have important clinical implications.

scholarly journals Chronic intermittent hypoxia in humans during 28 nights results in blood pressure elevation and increased muscle sympathetic nerve activity

2010 ◽  
Vol 299 (3) ◽  
pp. H925-H931 ◽  
Author(s):  
G. S. Gilmartin ◽  
M. Lynch ◽  
R. Tamisier ◽  
J. W. Weiss
Keyword(s):  
Blood Pressure ◽  
Sympathetic Nerve ◽  
Intermittent Hypoxia ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Chronic Intermittent Hypoxia ◽  
Sympathetic Activation ◽  
Nerve Activity ◽  
Blood Pressure Elevation ◽  
Healthy Humans

Chronic intermittent hypoxia (CIH) is thought to be responsible for the cardiovascular disease associated with obstructive sleep apnea (OSA). Increased sympathetic activation, altered vascular function, and inflammation are all putative mechanisms. We recently reported (Tamisier R, Gilmartin GS, Launois SH, Pepin JL, Nespoulet H, Thomas RJ, Levy P, Weiss JW. J Appl Physiol 107: 17–24, 2009) a new model of CIH in healthy humans that is associated with both increases in blood pressure and augmented peripheral chemosensitivity. We tested the hypothesis that exposure to CIH would also result in augmented muscle sympathetic nerve activity (MSNA) and altered vascular reactivity contributing to blood pressure elevation. We therefore exposed healthy subjects between the ages of 20 and 34 yr ( n = 7) to 9 h of nocturnal intermittent hypoxia for 28 consecutive nights. Cardiovascular and hemodynamic variables were recorded at three time points; MSNA was collected before and after exposure. Diastolic blood pressure (71 ± 1.3 vs. 74 ± 1.7 mmHg, P < 0.01), MSNA [9.94 ± 2.0 to 14.63 ± 1.5 bursts/min ( P < 0.05); 16.89 ± 3.2 to 26.97 ± 3.3 bursts/100 heartbeats (hb) ( P = 0.01)], and forearm vascular resistance (FVR) (35.3 ± 5.8 vs. 55.3 ± 6.5 mmHg·ml−1·min·100 g tissue, P = 0.01) all increased significantly after 4 wk of exposure. Forearm blood flow response following ischemia of 15 min (reactive hyperemia) fell below baseline values after 4 wk, following an initial increase after 2 wk of exposure. From these results we conclude that the increased blood pressure following prolonged exposure to CIH in healthy humans is associated with sympathetic activation and augmented FVR.

scholarly journals The influence of environmental and core temperature on cyclooxygenase and PGE2 in healthy humans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christopher J. Esh ◽  
Bryna C. R. Chrismas ◽  
Alexis R. Mauger ◽  
Anissa Cherif ◽  
John Molphy ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Skin Temperature ◽  
Effect Size ◽  
Mixed Models ◽  
Thermal Perception ◽  
Random Coefficient Models ◽  
Healthy Humans ◽  
Within Subjects ◽  
Thermogenic Response

AbstractWhether cyclooxygenase (COX)/prostaglandin E2 (PGE2) thermoregulatory pathways, observed in rodents, present in humans? Participants (n = 9) were exposed to three environments; cold (20 °C), thermoneutral (30 °C) and hot (40 °C) for 120 min. Core (Tc)/skin temperature and thermal perception were recorded every 15 min, with COX/PGE2 concentrations determined at baseline, 60 and 120 min. Linear mixed models identified differences between and within subjects/conditions. Random coefficient models determined relationships between Tc and COX/PGE2. Tc [mean (range)] increased in hot [+ 0.8 (0.4–1.2) °C; p < 0.0001; effect size (ES): 2.9], decreased in cold [− 0.5 (− 0.8 to − 0.2) °C; p < 0.0001; ES 2.6] and was unchanged in thermoneutral [+ 0.1 (− 0.2 to 0.4) °C; p = 0.3502]. A relationship between COX2/PGE2 in cold (p = 0.0012) and cold/thermoneutral [collapsed, condition and time (p = 0.0243)] was seen, with higher PGE2 associated with higher Tc. A within condition relationship between Tc/PGE2 was observed in thermoneutral (p = 0.0202) and cold/thermoneutral [collapsed, condition and time (p = 0.0079)] but not cold (p = 0.0631). The data suggests a thermogenic response of the COX/PGE2 pathway insufficient to defend Tc in cold. Further human in vivo research which manipulates COX/PGE2 bioavailability and participant acclimation/acclimatization are warranted to elucidate the influence of COX/PGE2 on Tc.

Short-term intermittent hypoxia enhances sympathetic responses to continuous hypoxia in humans

2007 ◽  
Vol 103 (3) ◽  
pp. 835-842 ◽  
Author(s):  
Urs A. Leuenberger ◽  
Cynthia S. Hogeman ◽  
Sadeq Quraishi ◽  
Latoya Linton-Frazier ◽  
Kristen S. Gray
Keyword(s):  
Blood Pressure ◽  
Sleep Apnea ◽  
Sympathetic Activity ◽  
Intermittent Hypoxia ◽  
Muscle Sympathetic Nerve Activity ◽  
Acute Hypoxia ◽  
Short Term ◽  
Healthy Humans ◽  
Obstructive Sleep ◽  
Normal Humans

Short-term intermittent hypoxia leads to sustained sympathetic activation and a small increase in blood pressure in healthy humans. Because obstructive sleep apnea, a condition associated with intermittent hypoxia, is accompanied by elevated sympathetic activity and enhanced sympathetic chemoreflex responses to acute hypoxia, we sought to determine whether intermittent hypoxia also enhances chemoreflex activity in healthy humans. To this end, we measured the responses of muscle sympathetic nerve activity (MSNA, peroneal microneurography) to arterial chemoreflex stimulation and deactivation before and following exposure to a paradigm of repetitive hypoxic apnea (20 s/min for 30 min; O2 saturation nadir 81.4 ± 0.9%). Compared with baseline, repetitive hypoxic apnea increased MSNA from 113 ± 11 to 159 ± 21 units/min ( P = 0.001) and mean blood pressure from 92.1 ± 2.9 to 95.5 ± 2.9 mmHg ( P = 0.01; n = 19). Furthermore, compared with before, following intermittent hypoxia the MSNA (units/min) responses to acute hypoxia [fraction of inspired O2 (FiO2) 0.1, for 5 min] were enhanced (pre- vs. post-intermittent hypoxia: +16 ± 4 vs. +49 ± 10%; P = 0.02; n = 11), whereas the responses to hyperoxia (FiO2 0.5, for 5 min) were not changed significantly ( P = NS; n = 8). Thus 30 min of intermittent hypoxia is capable of increasing sympathetic activity and sensitizing the sympathetic reflex responses to hypoxia in normal humans. Enhanced sympathetic chemoreflex activity induced by intermittent hypoxia may contribute to altered neurocirculatory control and adverse cardiovascular consequences in sleep apnea.

Resistive training increases fat-free mass and maintains RMR despite weight loss in postmenopausal women

1995 ◽  
Vol 79 (3) ◽  
pp. 818-823 ◽  
Author(s):  
A. S. Ryan ◽  
R. E. Pratley ◽  
D. Elahi ◽  
A. P. Goldberg
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Postmenopausal Women ◽  
Body Fat ◽  
Fat Mass ◽  
Management Program ◽  
Fat Free Mass ◽  
Percent Body Fat ◽  
Plasma Norepinephrine ◽  
Resistive Training

Percent body fat increases with age and is often accompanied by a loss in muscle mass, strength, and energy expenditure. The effects of 16 wk of resistive training (RT) alone or with weight loss (RTWL) on strength (isokinetic dynamometer), body composition (dual-energy X-ray absorptiometry), resting metabolic rate (RMR) (indirect calorimetry), and sympathetic nervous system activity (catecholamines) were examined in 15 postmenopausal women (50–69 yr). RT resulted in significant improvements in upper and lower body strength in both groups (P < 0.01). The nonobese women in the RT group (n = 8) did not change their body weight or fat mass with training. In the obese RTWL group (n = 7), body weight, fat mass, and percent body fat were significantly decreased (P < 0.001). Fat-free mass and RMR significantly increased with training in both groups combined (P < 0.05). There were no significant changes in resting arterialized plasma norepinephrine or epinephrine levels in either group with training. RT increases strength with and without weight loss. Furthermore, RT and RTWL increase fat-free mass and RMR and decrease percent fat in postmenopausal women. Thus, RT may be a valuable component of an integrated weight management program in postmenopausal women.

scholarly journals Short-term sprint interval training increases insulin sensitivity in healthy adults but does not affect the thermogenic response to β-adrenergic stimulation

2010 ◽  
Vol 588 (15) ◽  
pp. 2961-2972 ◽  
Author(s):  
Jennifer C. Richards ◽  
Tyler K. Johnson ◽  
Jessica N. Kuzma ◽  
Mark C. Lonac ◽  
Melani M. Schweder ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Interval Training ◽  
Healthy Adults ◽  
Sprint Interval Training ◽  
Adrenergic Stimulation ◽  
Short Term ◽  
Thermogenic Response

Neurocirculatory consequences of abrupt change in sleep state in humans

1996 ◽  
Vol 80 (5) ◽  
pp. 1627-1636 ◽  
Author(s):  
B. J. Morgan ◽  
D. C. Crabtree ◽  
D. S. Puleo ◽  
M. S. Badr ◽  
F. Toiber ◽  
...  
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Pressor Response ◽  
Muscle Sympathetic Nerve Activity ◽  
Intrathoracic Pressure ◽  
Nrem Sleep ◽  
Auditory Stimuli ◽  
Sleep State ◽  
Healthy Humans ◽  
Pressor Responses

The arterial pressure elevations that accompany sleep apneas may be caused by chemoreflex stimulation, negative intrathoracic pressure, and/or arousal. To assess the neurocirculatory effects of arousal alone, we applied graded auditory stimuli during non-rapid-eye-movement (NREM) sleep in eight healthy humans. We measured muscle sympathetic nerve activity (intraneural microelectrodes), electroencephalogram (EEG; C4/A1 and O1/A2), arterial pressure (photoelectric plethysmography), heart rate (electrocardiogram), and stroke volume (impedance cardiography). Auditory stimuli caused abrupt increases in systolic and diastolic pressures (21 +/- 2 and 15 +/- 1 mmHg) and heart rate (11 +/- 2 beats/min). Cardiac output decreased (-10%). Stimuli that produced EEG evidence of arousal evoked one to two large bursts of sympathetic activity (316 +/- 46% of baseline amplitude). Stimuli that did not alter EEG frequency produced smaller but consistent pressor responses even though no sympathetic activation was observed. We conclude that arousal from NREM sleep evokes a pressor response caused by increased peripheral vascular resistance. Increased sympathetic outflow to skeletal muscle may contribute to, but is not required for, this vasoconstriction. The neurocirculatory effects of arousal may augment those caused by asphyxia during episodes of sleep-disordered breathing.

Sign in / Sign up

Export Citation Format

Share Document