Grant H Simmons

University of Missouri, Columbia, Missouri, United States

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Publications (29)107.6 Total impact

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    ABSTRACT: Recent data suggests neuronal nitric oxide synthase (nNOS) mediates the NO-component of reflex cutaneous vasodilatation with passive heat stress. We tested the hypothesis that nNOS inhibition would attenuate reflex cutaneous vasodilatation during sustained dynamic exercise in young healthy humans. All subjects first performed an incremental V̇O2peak test to exhaustion on a custom-built supine cycle ergometer. On a separate day, subjects were instrumented with four intradermal microdialysis fibres on the forearm and each randomly assigned as: 1) lactated Ringer's (control); 2) 20 mM L-NAME (non-selective NOS inhibitor); 3) 5 mM NPLA (nNOS inhibitor); and 4) 10 mM L-NIO (eNOS inhibitor). Following microdialysis placement, subjects performed supine cycling with the experimental arm at heart level at 60% V̇O2peak for a duration sufficient to raise core temperature (TC) 0.8°C. At the end of cycling, all microdialysis sites were locally heated to 43°C and sodium nitroprusside was perfused to elicit maximal vasodilatation. Mean arterial pressure (MAP), skin blood flow via laser- Doppler flowmetry (LDF), and TC via ingestible telemetric pill were measured continuously; cutaneous vascular conductance (CVC) was calculated as LDF/MAP and normalized to maximum. There was no significant difference between control (58 ± 2 %CVCmax) and nNOS-inhibited (56 ± 3 %CVCmax) sites in response to exercise-induced hyperthermia. The increase in CVC at eNOS-inhibited (41 ± 3 %CVCmax) and nonselective NOS-inhibited (40 ± 4 %CVCmax) sites were significantly attenuated compared to control and nNOS-inhibited (P<0.001 all conditions) but there was no difference between eNOS-inhibited and nonselective NOS-inhibited sites. These data suggest eNOS, not nNOS, mediate NO synthesis during reflex cutaneous vasodilatation with sustained dynamic exercise.This article is protected by copyright. All rights reserved
    The Journal of Physiology 09/2014; 592(23). DOI:10.1113/jphysiol.2014.272898 · 4.38 Impact Factor
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    ABSTRACT: Exercise training has emerged as an intervention for the primary and secondary prevention of coronary artery disease, but the mechanisms through which training reduces relative risk are not completely understood. The goal of this study was to investigate the impact of endurance exercise training on vasomotor function and vascular cell phenotype in coronary arteries and systemic conduit arteries and veins against a background of advanced atherosclerosis. We tested the hypothesis that exercise training restores endothelial vasomotor function and produces an anti-atherogenic endothelial and smooth muscle cell phenotype in familial hypercholesterolemic (FH) swine. The study included 30 FH (15 EX, 15 SED) and 13 non-FH control male, castrated swine. The exercise training intervention consisted of treadmill running 5 days/wk for 16-20 wks. Tissues sampled at sacrifice included vascular rings from the coronary circulation for vasomotor function experiments (dose-dependent bradykinin-induced vasorelaxation) and ECs from isolated segments of the thoracic aorta, the carotid, brachial, femoral, and renal arteries, and each of these vessel's regionally associated vein, as well from the abdominal vena cava, the right coronary (RCA), and internal mammary arteries. Smooth muscle cells were sampled from the RCA only. Vascular cell phenotype was assessed by immunoblotting for a host of both pro- and anti- atherogenic markers (e.g., eNOS, p67phox, SOD-1, etc). Coronary artery endothelium-dependent vasomotor function was depressed in sedentary FH-pigs compared to sedentary controls, and exercise training did not change vasomotor function within FH. In contrast, only scattered effects of FH on EC phenotype were noted across the vasculature, which included both pro- and anti-atherogenic changes in EC protein expression (e.g., increased eNOS in carotid artery ECs, decreased p67phox in brachial artery ECs, but decreased expression of the antioxidant protein SOD1 in thoracic vena cava (all P<0.05)). In thoracic vena cava ECs, this deficit was corrected by EX, while no other effects of exercise were observed in conduit vessel EC phenotype. Thus, while EX abrogated the adverse effect of hypercholesterolaemia on thoracic vena cava SOD1 expression, it appears that EX does not produce a consistently improved EC phenotype in either coronary or systemic conduit vessels in this FH swine model.
    Experimental physiology 11/2013; 99(2). DOI:10.1113/expphysiol.2013.075838 · 2.87 Impact Factor
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    Grant H Simmons, Jaume Padilla, M Harold Laughlin
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    ABSTRACT: The purpose of this study was to investigate the extent of endothelial cell phenotypic heterogeneity throughout the swine vasculature, with a focus on the conduit vessels of the arterial and venous circulations. We tested the hypothesis that atheroprone arteries exhibit higher expression of markers of inflammation and oxidative stress than do veins and atheroresistant arteries. The study sample included tissues from 79 castrated, male swine. Immediately after the animals were killed, endothelial cells were mechanically scraped from isolated segments of the thoracic and abdominal aorta, carotid, brachial, femoral and renal arteries, and the vein regionally associated with each of these vessels, as well as the internal mammary and right coronary arteries. Cells were also taken from two regions of the aortic arch contrasted by atheroprone versus atherosusceptible haemodynamics. Endothelial cell phenotype was assessed by either immunoblotting or quantitative real-time PCR for a host of both pro- and anti-atherogenic markers (e.g. endothelial nitric oxide synthase, p67phox, cyclo-oxygenase-1 and superoxide dismutase 1). Marked heterogeneity across the vasculature was observed in the expression of both pro- and anti-atherogenic markers, at both the protein and transcriptional levels. In particular, the coronary vascular endothelium expressed higher levels of the oxidative stress marker p67phox (P < 0.05 versus other arteries). In addition, differential expression of endothelial nitric oxide synthase and KLF4 was evident between atheroprone and atherosusceptible regions of the aorta, while expression of endothelial nitric oxide synthase, KLF2, KLF4 and cyclo-oxygenase-1 was lower in both areas of the aortic arch compared with the internal mammary artery. Conduit arteries typically expressed higher levels of both pro- and anti-atherogenic markers relative to their associated veins. We show, for the first time, that endothelial cell phenotype is variable within vessels, across six major vascular territories, and between the arterial and venous circulations. Importantly, even straight vessel segments from systemic conduit arteries (e.g. brachial and carotid arteries) exhibited regional phenotypic heterogeneity; a finding not expected on the basis of local haemodynamic forces alone.
    Experimental physiology 04/2012; 97(9):1074-82. DOI:10.1113/expphysiol.2011.064006 · 2.87 Impact Factor
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    ABSTRACT: Blood flow (BF) increases with increasing exercise intensity in skeletal, respiratory, and cardiac muscle. In humans during maximal exercise intensities, 85% to 90% of total cardiac output is distributed to skeletal and cardiac muscle. During exercise BF increases modestly and heterogeneously to brain and decreases in gastrointestinal, reproductive, and renal tissues and shows little to no change in skin. If the duration of exercise is sufficient to increase body/core temperature, skin BF is also increased in humans. Because blood pressure changes little during exercise, changes in distribution of BF with incremental exercise result from changes in vascular conductance. These changes in distribution of BF throughout the body contribute to decreases in mixed venous oxygen content, serve to supply adequate oxygen to the active skeletal muscles, and support metabolism of other tissues while maintaining homeostasis. This review discusses the response of the peripheral circulation of humans to acute and chronic dynamic exercise and mechanisms responsible for these responses. This is accomplished in the context of leading the reader on a tour through the peripheral circulation during dynamic exercise. During this tour, we consider what is known about how each vascular bed controls BF during exercise and how these control mechanisms are modified by chronic physical activity/exercise training. The tour ends by comparing responses of the systemic circulation to those of the pulmonary circulation relative to the effects of exercise on the regional distribution of BF and mechanisms responsible for control of resistance/conductance in the systemic and pulmonary circulations. © 2012 American Physiological Society. Compr Physiol 2:321-447, 2012.
    01/2012; 2(1):321-447. DOI:10.1002/cphy.c100048
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    ABSTRACT: The objective of this study was to develop transgenic Yucatan minipigs that overexpress human catalase (hCat) in an endothelial-specific manner. Catalase metabolizes hydrogen peroxide (H(2)O(2)), an important regulator of vascular tone that contributes to diseases such as atherosclerosis and preeclampsia. A large animal model to study reduced endothelium-derived H(2)O(2) would therefore generate valuable translational data on vascular regulation in health and disease. Yucatan minipig fetal fibroblasts stably co-transfected with human catalase (Tie2-hCat) and eGFP expression constructs were isolated into single-cell populations. The presence of the Tie2-hCat transgene in individual colonies of fibroblasts was determined by PCR. Transgenic fibroblasts were used for nuclear transfer into enucleated oocytes by electrofusion. A minimum of 140 cloned embryos were transferred per surrogate sow (n = 4). All four surrogates maintained pregnancies and piglets were delivered by cesarean section. Nine male piglets from three of the four litters carried the Tie2-hCat transgene. Expression of human catalase mRNA and overall elevated catalase protein in isolated umbilical endothelial cells from transgenic piglets were verified by RT-PCR and western blot, respectively, and endothelial localization was confirmed by immunohistochemistry. Increased enzymatic activity of catalase in transgenic versus wild-type endothelial cells was inferred based on significantly reduced levels of H(2)O(2) in culture. The similarities in swine and human cardiovascular anatomy and physiology will make this pig model a valuable source of information on the putative role of endothelium-derived H(2)O(2) in vasodilation and in the mechanisms underlying vascular health and disease.
    Transgenic Research 10/2011; 20(5):989-1001. DOI:10.1007/s11248-010-9473-7 · 2.28 Impact Factor
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    ABSTRACT: We recently observed a marked increase in brachial artery (BA) diameter during prolonged leg cycling exercise. The purpose of the present study was to test the hypothesis that this increase in BA diameter during lower limb exercise is shear stress mediated. Accordingly, we determined whether recapitulation of cycling-induced BA shear rate with forearm heating, a known stimulus evoking shear-induced conduit artery dilatation, would elicit comparable profiles and magnitudes of BA vasodilatation to those observed during cycling. In 12 healthy men, BA diameter and blood velocity were measured simultaneously using Doppler ultrasonography at baseline and every 5 min during 60 min of either steady-state semi-recumbent leg cycling (120 W) or forearm heating. At the onset of cycling, the BA diameter was reduced (-3.9 ± 1.2% at 5 min; P < 0.05), but it subsequently increased throughout the remainder of the exercise bout (+15.1 ± 1.6% at 60 min; P < 0.05). The increase in BA diameter during exercise was accompanied by an approximately 2.5-fold rise in BA mean shear rate (P < 0.05). Similar increases in BA mean shear with forearm heating elicited an equivalent magnitude of BA vasodilatation to that observed during cycling (P > 0.05). Herein, we found that in the absence of exercise the extent of the BA vasodilator response was reproduced when the BA was exposed to comparable magnitudes of shear rate via forearm heating. These results are consistent with the hypothesis that shear stress plays a key role in signalling brachial artery vasodilatation during dynamic leg exercise.
    Experimental physiology 07/2011; 96(10):1019-27. DOI:10.1113/expphysiol.2011.059584 · 2.87 Impact Factor
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    ABSTRACT: We tested the effect of hypoxia on cutaneous vascular regulation and defense of core temperature during cold exposure. Twelve subjects had two microdialysis fibres placed in the ventral forearm and were immersed to the sternum in a bathtub on parallel study days (normoxia and poikilocapnic hypoxia with an arterial O(2) saturation of 80%). One fibre served as the control (1 mM propranolol) and the other received 5 mM yohimbine (plus 1 mM propranolol) to block adrenergic receptors. Skin blood flow was assessed at each site (laser Doppler flowmetry), divided by mean arterial pressure to calculate cutaneous vascular conductance (CVC), and scaled to baseline. Cold exposure was first induced by a progressive reduction in water temperature from 36 to 23°C over 30 min to assess cutaneous vascular regulation, then by clamping the water temperature at 10°C for 45 min to test defense of core temperature. During normoxia, cold stress reduced CVC in control (-44 ± 4%) and yohimbine sites (-13 ± 7%; both P < 0.05 versus precooling). Hypoxia caused vasodilatation prior to cooling but resulted in greater reductions in CVC in control (-67 ± 7%) and yohimbine sites (-35 ± 11%) during cooling (both P < 0.05 versus precooling; both P < 0.05 versus normoxia). Core cooling rate during the second phase of cold exposure was unaffected by hypoxia (-1.81 ± 0.23°C h(-1) in normoxia versus -1.97 ± 0.33°C h(-1) in hypoxia; P > 0.05). We conclude that hypoxia increases cutaneous (non-noradrenergic) vasoconstriction during prolonged cold exposure, while core cooling rate is not consistently affected.
    Experimental physiology 06/2011; 96(10):1062-71. DOI:10.1113/expphysiol.2011.059147 · 2.87 Impact Factor
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    ABSTRACT: Endothelial adaptations to exercise training are not exclusively conferred within the active muscle beds. Herein, we summarize key studies that have evaluated the impact of chronic exercise on the endothelium of vasculatures perfusing nonworking skeletal muscle, brain, viscera, and skin, concluding with discussion of potential mechanisms driving these endothelial adaptations.
    Physiology 06/2011; 26(3):132-45. DOI:10.1152/physiol.00052.2010 · 6.75 Impact Factor
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    ABSTRACT: While the salutary effects of exercise training on conduit artery endothelial cells have been reported in animals and humans with cardiovascular risk factors or disease, whether a healthy endothelium is alterable with exercise training is less certain. The purpose of this study was to evaluate the impact of exercise training on transcriptional profiles in normal endothelial cells using a genome-wide microarray analysis. Brachial and internal mammary endothelial gene expression was compared between a group of healthy pigs that exercise trained for 16-20 wk (n = 8) and a group that remained sedentary (n = 8). We found that a total of 130 genes were upregulated and 84 genes downregulated in brachial artery endothelial cells with exercise training (>1.5-fold and false discovery rate <15%). In contrast, a total of 113 genes were upregulated and 31 genes downregulated in internal mammary artery endothelial cells using the same criteria. Although there was an overlap of 66 genes (59 upregulated and 7 downregulated with exercise training) between the brachial and internal mammary arteries, the identified endothelial gene networks and biological processes influenced by exercise training were distinctly different between the brachial and internal mammary arteries. These data indicate that a healthy endothelium is indeed responsive to exercise training and support the concept that the influence of physical activity on endothelial gene expression is not homogenously distributed throughout the vasculature.
    AJP Heart and Circulatory Physiology 05/2011; 301(2):H555-64. DOI:10.1152/ajpheart.00065.2011 · 4.01 Impact Factor
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    ABSTRACT: Heat is the most abundant byproduct of cellular metabolism. As such, dynamic exercise in which a significant percentage of muscle mass is engaged generates thermoregulatory demands that are met in part by increases in skin blood flow. Increased skin blood flow during exercise adds to the demands on cardiac output and confers additional circulatory strain beyond that associated with perfusion of active muscle alone. Endurance exercise training results in a number of physiological adaptations which ultimately reduce circulatory strain and shift thermoregulatory control of skin blood flow to higher levels of blood flow for a given core temperature. In addition, exercise training induces peripheral vascular adaptations within the cutaneous microvasculature indicative of enhanced endothelium-dependent vasomotor function. However, it is not currently clear how (or if) these local vascular adaptations contribute to the beneficial changes in thermoregulatory control of skin blood flow following exercise training. The purpose of this Hot Topic Review is to synthesize the literature pertaining to exercise training-mediated changes in cutaneous microvascular reactivity and thermoregulatory control of skin blood flow. In addition, we address mechanisms driving changes in cutaneous microvascular reactivity and thermoregulatory control of skin blood flow, and pose the question: what (if any) is the functional role of increased cutaneous microvascular reactivity following exercise training?
    Experimental physiology 05/2011; 96(9):822-8. DOI:10.1113/expphysiol.2010.056176 · 2.87 Impact Factor
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    Grant H Simmons, Shawn B Bender
    The Journal of Physiology 05/2011; 589(Pt 10):2437-8. DOI:10.1113/jphysiol.2011.208751 · 4.38 Impact Factor
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    ABSTRACT: Brachial artery flow-mediated dilation (FMD) is a strong predictor of future cardiovascular disease and is believed to represent a "barometer" of systemic endothelial health. Although a recent study [Padilla et al. Exp Biol Med (Maywood) 235: 1287-1291, 2010] in pigs confirmed a strong correlation between brachial and femoral artery endothelial function, it is unclear to what extent brachial artery FMD represents a systemic index of endothelial function in humans. We conducted a retrospective analysis of data from our laboratory to evaluate relationships between the upper (i.e., brachial artery) vs. lower limb (superficial femoral n = 75; popliteal artery n = 32) endothelium-dependent FMD and endothelium-independent glyceryl trinitrate (GTN)-mediated dilation in young, healthy individuals. We also examined the relationship between FMD assessed in both brachial arteries (n = 42). There was no correlation between brachial and superficial femoral artery FMD (r(2) = 0.008; P = 0.46) or between brachial and popliteal artery FMD (r(2) = 0.003; P = 0.78). However, a correlation was observed in FMD between both brachial arteries (r(2) = 0.34; P < 0.001). Brachial and superficial femoral artery GTN were modestly correlated (r(2) = 0.13; P = 0.007), but brachial and popliteal artery GTN responses were not (r(2) = 0.08; P = 0.11). Collectively, these data indicate that conduit artery vasodilator function in the upper limbs (of healthy humans) is not predictive of that in the lower limbs, whereas measurement of FMD in one arm appears to be predictive of FMD in the other. These data do not support the hypothesis that brachial artery FMD in healthy humans represents a systemic index of endothelial function.
    Journal of Applied Physiology 04/2011; 111(1):244-50. DOI:10.1152/japplphysiol.00290.2011 · 3.43 Impact Factor
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    ABSTRACT: Aging has been recently associated with increased retrograde and oscillatory shear in peripheral conduit arteries, a hemodynamic environment that favors a proatherogenic endothelial cell phenotype. We evaluated whether nitric oxide (NO) bioavailability in resistance vessels contributes to age-related differences in shear rate patterns in upstream conduit arteries at rest and during rhythmic muscle contraction. Younger (n=11, age 26 ± 2 years) and older (n=11, age 61 ± 2 years) healthy subjects received intra-arterial saline (control) and the NO synthase inhibitor N(G)-Monomethyl-L-arginine. Brachial artery diameter and velocities were measured via Doppler ultrasound at rest and during a 5-minute bout of rhythmic forearm exercise. At rest, older subjects exhibited greater brachial artery retrograde and oscillatory shear (-13.2 ± 3.0 s(-1) and 0.11 ± .0.02 arbitrary units, respectively) compared with young subjects (-4.8 ± 2.3 s(-1) and 0.04 ± 0.02 arbitrary units, respectively; both P<0.05). NO synthase inhibition in the forearm circulation of young, but not of older, subjects increased retrograde and oscillatory shear (both P<0.05), such that differences between young and old at rest were abolished (both P>0.05). From rest to steady-state exercise, older subjects decreased retrograde and oscillatory shear (both P<0.05) to the extent that no exercise-related differences were found between groups (both P>0.05). Inhibition of NO synthase in the forearm circulation did not affect retrograde and oscillatory shear during exercise in either group (all P>0.05). These data demonstrate for the first time that reduced NO bioavailability in the resistance vessels contributes, in part, to age-related discrepancies in resting shear patterns, thus identifying a potential mechanism for increased risk of atherosclerotic disease in conduit arteries.
    Hypertension 03/2011; 57(3):484-9. DOI:10.1161/HYPERTENSIONAHA.110.165365 · 7.63 Impact Factor
  • Grant H. Simmons, Jaume Padilla, M. Harold Laughlin
    Medicine &amp Science in Sports &amp Exercise 01/2011; 43(Suppl 1):155. DOI:10.1249/01.MSS.0000400406.41241.78 · 4.46 Impact Factor
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    ABSTRACT: Acute leg exercise increases brachial artery retrograde shear rate (SR), while chronic exercise improves vasomotor function. These combined observations are perplexing given the proatherogenic impacts of retrograde shear stress on the vascular endothelium and may be the result of brief protocols used to study acute exercise responses. Therefore, we hypothesized that brachial artery retrograde SR increases initially but subsequently decreases in magnitude during prolonged leg cycling. Additionally, we tested the role of cutaneous vasodilation in the elimination of increased retrograde SR during prolonged exercise. Brachial artery diameter and velocity profiles and forearm skin blood flow and temperature were measured at rest and during 50 min of steady-state, semirecumbent leg cycling (120 W) in 14 males. Exercise decreased forearm vascular conductance (FVC) and increased retrograde SR at 5 min (both P < 0.05), but subsequently forearm and cutaneous vascular conductance (CVC) rose while retrograde SR returned toward baseline values. The elimination of increased retrograde SR was related to the increase in FVC (r(2) = 0.58; P < 0.05) and CVC (r(2) = 0.32; P < 0.05). Moreover, when the forearm was cooled via a water-perfused suit between minutes 30 and 40 to blunt cutaneous vasodilation attending exercise, FVC was reduced and the magnitude of retrograde SR was increased from -49.7 ± 13.6 to -78.4 ± 16.5 s(-1) (P < 0.05). Importantly, these responses resolved with removal of cooling during the final 10 min of exercise (retrograde SR: -46.9 ± 12.5 s(-1)). We conclude that increased brachial artery retrograde SR at the onset of leg cycling subsequently returns toward baseline values due in part to thermoregulatory cutaneous vasodilation during prolonged exercise.
    Journal of Applied Physiology 11/2010; 110(2):389-97. DOI:10.1152/japplphysiol.00936.2010 · 3.43 Impact Factor
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    ABSTRACT: In humans, the measurement of brachial artery endothelial vasomotor function is used as a surrogate index of systemic endothelial health; however, the applicability of brachial artery findings to other vasculatures needs to be examined. The purpose of the present investigation was to test the following hypotheses: (1) brachial and femoral artery endothelium-dependent/independent relaxation is correlated; (2) endothelial expression of pro-/antiatherogenic proteins is correlated between brachial and femoral arteries; and (3) within vessel, there is a positive correlation between expression of antiatherogenic proteins and endothelium-dependent/independent relaxation, and an inverse correlation between expression of proatherogenic proteins and relaxation. In vitro endothelium-dependent (bradykinin [BK] and acetylcholine [Ach]) and -independent (sodium nitroprusside [SNP]) relaxation were evaluated in harvested brachial and femoral arteries of 96 Yucatan miniature swine. In a subset of pigs (n = 32), expression of 18 pro-/antiatherogenic proteins was measured from brachial and femoral artery endothelial cell scrapes using immunoblot analysis. Vascular sensitivity (half-maximal effective dose) to BK, Ach and SNP was highly correlated between brachial and femoral arteries (P < 0.01). A significant correlation was found between brachial and femoral arteries for content of six of the 18 measured proteins (P < 0.01). Furthermore, expression of two proteins (eNOS and COX-1) was correlated with vasorelaxation function in the brachial artery (P < 0.01). We provide the first evidence of a relationship between brachial and femoral artery endothelium-dependent relaxation. Our data also suggest that, in general terms, endothelial expression of several established pro-/antiatherogenic proteins is not robustly associated between brachial and femoral arteries, and does not link strongly to vasorelaxation function.
    Experimental Biology and Medicine 11/2010; 235(11):1287-91. DOI:10.1258/ebm.2010.010148 · 2.23 Impact Factor
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    ABSTRACT: Elevated blood flow can potentially influence skeletal muscle glucose uptake, but the impact of postexercise hyperemia on glucose availability to skeletal muscle remains unknown. Because postexercise hyperemia is mediated by histamine H(1)- and H(2)-receptors, we tested the hypothesis that postexercise interstitial glucose concentrations would be lower in the presence of combined H1- and H2-receptor blockade. To this end, 4 microdialysis probes were inserted into the vastus lateralis muscle of 14 healthy subjects (21-27 years old) immediately after 60 min of either upright cycling at 60% peak oxygen uptake (exercise, n = 7) or quiet rest (sham, n = 7). Microdialysis probes were perfused with a modified Ringer's solution containing 3 mmol L(-1) glucose, 5 mmol L(-1) ethanol, and [6-3H] glucose (200 disintegrations·min-1 microL(-1)). Two sites (blockade) received both H1- and H2-receptor antagonists (1 mmol L(-1) pyrilamine and 3 mmol L-1 cimetidine) and 2 sites (control) did not receive antagonists. Ethanol outflow/inflow ratios (an inverse surrogate of local blood flow) were higher in blockade sites than in control sites following exercise (p < 0.05), whereas blockade had no effect on ethanol outflow/inflow ratios following sham (p = 0.80). Consistent with our hypothesis, during 3 of the 5 dialysate collection periods, interstitial glucose concentrations were lower in blockade sites vs. control sites following exercise (p < 0.05), whereas blockade had no effect on interstitial glucose concentrations following sham (p = 0.79). These findings indicate that local H1- and H2-receptor activation modulates skeletal muscle interstitial glucose levels during recovery from exercise in humans and suggest that the availability of glucose to skeletal muscle is enhanced by postexercise hyperemia.
    Applied Physiology Nutrition and Metabolism 10/2010; 35(5):617-26. DOI:10.1139/H10-055 · 2.23 Impact Factor
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    ABSTRACT: Hypoxia impairs body temperature regulation and abolishes the decline in skin temperature associated with cold exposure, suggesting that cutaneous vasoconstriction is impaired. The purpose of this study was to test the hypothesis that cutaneous vasoconstriction to intradermal tyramine, an index of post-junctional vasoconstrictor responsiveness, is reduced during hypoxia. Twelve subjects (six males, six females) had three microdialysis fibres placed in the ventral forearm. Fibres received either lactated ringers, 5 mm yohimbine (α-adrenergic blockade), or 10.5 μm BIBP-3226 (to antagonize neuropeptide Y Y(1) receptors). Skin blood flow was assessed at each site (laser-Doppler flowmetry) and cutaneous vascular conductance (CVC) was calculated (red blood cell flux/mean arterial pressure) and scaled to baseline. Vasoconstrictor responses to tyramine (173 μm) were tested during normoxia and steady-state isocapnic hypoxia (SaO(2) = 80%) in random order. During normoxia, tyramine reduced CVC by 56.0±5.6 and 50.3±8.0% in control and BIBP-3226 sites (both P<0.05 vs. pre-tyramine; P=0.445 between sites) whereas CVC in the yohimbine site did not change (P=0.398 vs. pre-tyramine). During isocapnic hypoxia, tyramine reduced CVC by 55.9±5.1 and 54.2±5.4% in control and BIBP-3226 sites (both P<0.05 vs. pre-tyramine; P=0.814 between sites) whereas CVC was unchanged in the yohimbine site (P=0.732 vs. pre-tyramine). Isocapnic hypoxia did not affect vasoconstrictor responses at any site (all P>0.05 vs. normoxia). We conclude that post-junctional α-adrenergic vasoconstrictor responsiveness is not affected by hypoxia in non-acral skin.
    Acta Physiologica 10/2010; 201(3):339-47. DOI:10.1111/j.1748-1716.2010.02193.x · 4.25 Impact Factor
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    ABSTRACT: Although the beneficial effects of exercise training on conduit artery endothelial function are well-established in animals and humans with compromised basal function, whether exercise exerts favorable effects on a healthy endothelium is inconclusive. We sought to determine whether long-term exercise training enhances endothelial function in peripheral conduit arteries of healthy pigs. Using a retrospective analysis of data collected in our laboratory (n = 127), we compared in vitro brachial and femoral artery endothelium-dependent and -independent relaxation between a group of pigs that exercise-trained for 16-20 wk and a group that remained sedentary. No differences in vasomotor function were found between the 2 groups (P > 0.05). Additionally, in a subset of pigs (n = 16), expression levels of 18 proteins that are typically associated with the atherosclerotic process were measured by immunoblot analysis of endothelial cell scrapes obtained from the brachial and femoral arteries. We found no differences (P > 0.05) in endothelial gene expression between these exercise-trained and sedentary healthy pigs. These results indicate that pigs exhibiting the classic training-induced adaptations do not demonstrate enhanced endothelium-dependent dilation nor reveal a more atheroprotected endothelial cell phenotype in their brachial and femoral arteries than their sedentary but otherwise healthy counterparts.
    AJP Heart and Circulatory Physiology 08/2010; 299(2):H379-85. DOI:10.1152/ajpheart.00294.2010 · 4.01 Impact Factor
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    Grant H Simmons, Jaume Padilla
    The Journal of Physiology 07/2010; 588(Pt 14):2527-8. DOI:10.1113/jphysiol.2010.191882 · 4.38 Impact Factor