| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Noll Physiological Research Center2 Department of Kinesiology, The Pennsylvania State University, University Park, PA 16802-6900, USA
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
CVCbase). Solutions of yohimbine + propranolol (Y + P), bretylium tosylate (BT), and lactated Ringer solution were infused via intradermal microdialysis at each LDF site to antagonize 
- and ß-adrenoceptors, block sympathetic release of NA and cotransmitters, and act as control, respectively. During cooling, VC was attenuated at the control site in older subjects compared to young subjects (–16 ± 3 versus–34 ± 4%CVCbase, P < 0.001). Y + P attenuated VC in young subjects (–13 ± 8%CVCbase, P < 0.001 versus control) and abolished VC in older subjects (0 ± 3%CVCbase, P > 0.9 versus baseline). BT completely blocked VC in both age groups. Cutaneous VC in young subjects is mediated by both NA and sympathetic cotransmitter(s); however, reflex VC in aged skin is attenuated compared to young and appears to be mediated solely by NA.
(Received 2 April 2004;
accepted after revision 28 May 2004;
first published online 4 June 2004)
Corresponding author W. L. Kenney: The Pennsylvania State University, 119 Noll Laboratory, University Park, PA 16802, USA. Email: w7k{at}psu.edu
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Several studies have demonstrated that there are both noradrenaline (NA)-mediated and non-NA-mediated VC mechanisms of sympathetic origin in thermoregulatory cutaneous circulations in animal models and in humans (Morris, 1999; Racchi et al. 1999; Stephens et al. 2001, 2002a; Bradley et al. 2003). If non-NA VC function, mediated by sympathetic cotransmitters, is compromised with age, this may explain the attenuated cutaneous VC in older subjects during cooling. Lambert et al. (1999) demonstrated that cutaneous venoconstrictor responses to infusions of the putative sympathetic cotransmitter neuropeptide Y (NPY) in older humans are attenuated compared to responses seen in young subjects. When these results are considered in light of the findings of Dhall et al. (1986) and Connat et al. (2001), which indicate that peptidergic innervation in several vascular beds may be reduced with age, the combined evidence suggests that the effectiveness of cotransmitter-mediated VC in the skin may be reduced with age, as well.
The purpose of the present study was to determine the relative contribution of cotransmitter-mediated mechanisms to reflex cutaneous VC in young and older subjects in response to whole-body cooling. Specifically, the present study tested the hypothesis that age-related changes in cotransmitter-mediated mechanisms contribute significantly to the attenuated reflex VC observed in older subjects.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Fifteen young (18–29 years; seven men, eight women) and 12 older (60–77 years; six men, six women) subjects participated in the present study. All young women were tested during the early follicular phase of the menstrual cycle and were not taking oral contraceptives; all older women were postmenopausal and were not taking hormone replacement therapy. All subjects underwent a standardized medical screening and were healthy, normotensive, and non-obese. No subjects smoked nor were taking any medications which might alter cardiovascular responses to cooling. They abstained from alcohol and caffeine for 12 h prior to coming to the laboratory for the study but were permitted to eat a modest breakfast the morning of the experiment. Approval was obtained from the Institutional Review Board of The Pennsylvania State University. Each subject gave written informed consent prior to participation in the study, and all procedures conformed to the standards of the Declaration of Helsinki.
Instrumentation
Subjects arrived at the laboratory on the morning of the experiment and dressed in a water-perfused suit that was used to control skin temperature during the protocol. The suit covered the entire body except for the feet, head, hands, and forearms. Whole-body skin temperature was measured by six thermocouples placed on the calf, thigh, abdomen, back, chest, and upper arm. Mean skin temperature (Tsk) was calculated as the unweighted average of temperatures from these six sites.
Three microdialysis (MD) fibres (MD-2000, Bioanalytical Systems, West Lafayette, IN, USA) were placed into the ventral surface of the right forearm using sterile technique. Before the fibres were placed, an ice pack was applied to the MD sites for 5 min to temporarily anaesthetize the skin. For each fibre, a 25-gauge needle was inserted into the dermis and guided horizontally through the skin such that entry and exit points were approximately 2 cm apart. The fibre, consisting of a 10 mm membrane (320 µm outer diameter, 20 kDa molecular mass cut-off) and connective tubing attached to either end of the membrane, was threaded through the needle. The needle was then withdrawn, leaving the membrane in the skin. After insertion of all fibres, subjects rested quietly for approximately 90 min to allow local hyperaemia due to insertion trauma to subside.
SkBF was measured using laser Doppler flowmetry (LDF; DRT4 and MoorLAB, Moor Instruments, UK); LDF probes were placed directly over each microdialysis membrane, and LDF data were collected continuously throughout the experiment. Arterial blood pressure was monitored every 6 min throughout the experiment via brachial auscultation, and mean arterial pressure (MAP) was calculated as [(1/3 x systolic blood pressure) + (2/3 x diastolic blood pressure)]. SkBF was expressed as cutaneous vascular conductance (CVC), which was calculated as the ratio of LDF flux to MAP, and expressed as percentage change from baseline values (%CVCbase).
Protocol
After the MD fibres were in place, lactated Ringer solution was infused through all fibres at a rate of 2 µl min–1 using a microinfusion pump (Harvard 22, South Natick, MA, USA) for approximately 90 min. In a subset of subjects (eight young, nine older), a 40 mM solution of bretylium tosylate (BT; ICN Biomedicals Inc., Aurora, OH, USA) was infused at one of the MD sites at this time to block the presynaptic release of neurotransmitters from adrenergic nerve terminals. During this equilibration period while local hyperaemia subsided and BT took effect, thermoneutral water was circulated through the suit so that Tsk was clamped at 34°C. After SkBF returned to baseline steady-state values, ice water was circulated through the suit for three minutes to induce reflex VC, testing the integrity of the sympathetic presynaptic antagonism at the BT site.
Following the brief bout of cooling, thermoneutral water was again circulated through the suit. At this time, a solution of 5 mM yohimbine + 1 mM propranolol (Y + P; Sigma Chemical, St Louis, MO, USA) was infused at a second MD site. At these concentrations, Y + P antagonizes the postsynaptic effects of NA at - and ß-adrenoceptors. Yohimbine, typically an 2-adrenoceptor-specific antagonist, was used in a relatively high concentration in the present study to act as a non-specific -adrenoceptor antagonist, because previous studies (Goldberg & Robertson, 1983; Stephens et al. 2001, 2002a) and pilot work for the present study indicate that yohimbine in high concentrations is effective as a non-specific -adrenoceptor antagonist in human skin. The final MD site remained infused with only lactated Ringer solution to serve as control. Y + P was infused for approximately 60–75 min, at which point prolonged whole-body cooling commenced. Tsk was reduced from 34 to 30.5°C over a period of 30 min and was then clamped at 30.5°C for an additional 15 min. Rewarming followed.
After Tsk recovered from cooling and SkBF again reached a steady state, solutions of 100 µM NA (Sigma) + pre-existing antagonists were infused at all MD sites for 10 min to test the integrity of the Y + P adrenoceptor antagonism. All drugs in the present study were mixed just prior to usage, dissolved in lactated Ringer solution and sterilized using syringe microfilters (Acrodisc, Pall, Ann Arbor, MI, USA).
Data collection and analysis
Data were recorded and stored as 1 min averages using data acquisition computer software (LabView). CVC values recorded during cooling were averaged over 0.5°C intervals for analysis; CVC values recorded after Tsk was clamped were divided into 5 min segments and averaged within those time segments for analysis. All CVC data obtained during NA infusion as well as during prolonged whole-body cooling at control and Y + P sites were analysed using three-way analyses of variance (ANOVA) with repeated measures followed by Tukey-Kramer post hoc comparisons when significant differences were detected. BT site data obtained during prolonged whole-body cooling were analysed using two-way ANOVA with repeated measures followed by Tukey-Kramer post hoc comparisons when significant differences were detected. Statistical significance was set at = 0.05. Values are expressed at means ±S.E.M., unless otherwise noted.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
|
CVCbase, P < 0.001). At the Y + P site, where all VC effects of NA were blocked (see Fig. 2), significant yet attenuated VC was observed in young subjects (–13 ± 8%CVCbase, P < 0.001 versus control and baseline), while older subjects exhibited no VC at any point during cooling (0 ± 3%CVCbase, P > 0.9 versus baseline). At the BT-treated site, where the sympathetic release of axon contents was blocked, there was no significant VC observed in either age group (P > 0.9).
|
|
CVCbase, older: –35 ± 6%CVCbase; P < 0.001 versus baseline). In contrast, there was no VC observed at the Y + P site in either group of subjects with NA infusion (young: 0 ± 2%CVCbase, older: 1 ± 2%CVCbase, P > 0.9 versus baseline). There were no significant age differences at either site.
In Fig. 3A, CVC responses in young subjects at all three MD sites over the full 10 min NA infusion are presented. VC was observed at the control site (–51 ± 6%CVCbase, P < 0.0001 versus baseline), while no significant reduction in CVC was observed at any time during application of NA at the Y + P site. Significant VC was observed at the BT site (–20 ± 6%CVCbase, P < 0.01); however, VC was delayed, and the magnitude of VC was significantly attenuated compared with VC observed at the control site (P < 0.0001).
|
CVCbase, P < 0.0001), while no significant VC from baseline was observed at either Y + P or BT sites (P > 0.9) at any point during the NA infusion. The degree and time course of VC at BT sites also followed age-specific patterns: older subjects' VC responses at both sites were significantly different from those of the young subjects during the last 6 min of NA infusion (P < 0.05), and three-way ANOVA revealed a significant age x site x time interaction (P= 0.0003), indicating that NA induced different site-dependent patterns of VC between young and older groups. |
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Young subjects
Our conclusion that reflex cutaneous VC in young humans is due to both NA and (an)other cotransmitter(s) corroborates the findings of other investigators (Taddei et al. 1990; Racchi et al. 1999; Stephens et al. 2001, 2002a). Cumulatively, these studies and the present study confirm that significant non-NA-mediated VC persists in the presence of full adrenoceptor antagonism, suggesting a considerable cotransmitter contribution to reflex cutaneous VC. In the young subjects tested in the present study, BT treatment blocked the entire VC response, while combined treatment of Y + P blocked only 60% of the VC response to cooling. Together, these data indicate that (1) reflex VC is fully accounted for by sympathetic mechanisms, and (2) cotransmitter mechanisms account for 
40% of reflex VC.
Although the mediators and specific characteristics of cotransmission may vary among vascular beds, both NPY and adenosine triphosphate (ATP) have been identified as possible sympathetic cotransmitters contributing to the reflex VC response in many vascular beds, including human skin. NPY is produced, costored, and coreleased with NA from sympathetic adrenergic perivascular nerve terminals (Ekblad et al. 1984; Fried et al. 1985; Lundberg et al. 1990). It has a dual role of both mediating direct VC and potentiating NA-mediated VC through postsynaptic Y1 receptors in a number of tissues, including human skin (Wahlestedt et al. 1990; Nilsson et al. 1996; Racchi et al. 1997, 1999; Han et al. 1998; Stephens et al. 2002b). ATP is commonly costored with NA in small vesicles (compared to NA–NPY costorage in large, dense-core vesicles) in many sympathetic adrenergic nerves (Lundberg, 1996; Burnstock, 1999). ATP participates in VC responses to low-frequency electrical nerve stimulation (Ralevic & Burnstock, 1991; Racchi et al. 1999; García-Villalón et al. 2000; Bradley et al. 2003) and lower body negative pressure (Taddei et al. 1990) in thermoregulatory cutaneous circulations; this VC is mediated by P2X purinoceptors, which are found on vascular smooth muscle. Together, these studies suggest that NPY and/or ATP may actively function as cotransmitters in young human skin.
The finding from the present study that there were no sex differences in young subjects' VC responses to cooling seemingly conflicts with the findings of Stephens et al. (2002a), which demonstrated that sympathetic cotransmitters did not significantly participate in reflex VC in young women during low reproductive hormone phases. In that study, VC responses to cooling were recorded on young women who were taking oral contraceptives – once at the end of the high hormone phase and again at the end of the placebo week (low hormone phase). In contrast, the young female subjects in the present study were normally menstruating young women who were not taking oral contraceptives and were tested during the early follicular phase of the menstrual cycle. Stachenfeld et al. (2000) demonstrated that subtle differences in thermoregulatory function exist between women tested while taking oral contraceptives and women tested in the absence of exogenous hormones. Thus, although the women in both the present study and the study by Stephens et al. were tested during low hormone phases, it is possible that the control of skin blood flow was altered by the presence or absence of oral contraceptive use.
Age differences
Our data indicate that the attenuated VC response in older subjects is due in large part to the loss of cotransmitter-mediated VC during cooling. Relatively little information is available regarding why and how cotransmitters change with age in humans, but there are several possible points at which ageing may compromise cotransmitter production and/or activity. First, the rate of synthesis of cotransmitters within the neurone may decline with ageing. Evidence from animal models suggests that peptidergic innervation in the vascular wall decreases with ageing (Dhall et al. 1986; Connat et al. 2001); while these studies specifically examined neuropeptide cotransmitters, it is possible that other cotransmitters may be similarly affected with advancing age (Lundberg, 1996). In contrast, if the rate of cotransmitter synthesis is unaffected by age in humans, it is unlikely that the rate of release of cotransmitters from sympathetic axon terminals would be affected. NA is stored with cotransmitters in both small and large, dense-core vesicles (Bartfai et al. 1988; Lundberg, 1996) and is released with cotransmitters in response to nerve stimulation. Yet NA release is not attenuated with age (Hogikyan & Supiano, 1994; Landsberg, 1994; Dinenno et al. 2002), implying that cotransmitter release may not be attenuated, either.
It is possible that cotransmitter receptor number or down-stream intracellular regulators of VC may be altered with age. Lambert et al. (1999) infused incremental doses of NPY into cutaneous hand veins of young and older humans and found that dose–response curves were significantly shifted to the right in the older subjects, indicating an attenuated VC response to NPY. Likewise, Konishi et al. (1999) administered increasing doses of ATP to isolated vessels from young and old rats and concluded that ATP-mediated VC is compromised with advancing age. From the results of these two studies, it is not possible to definitively establish whether receptor number or down-stream signal transduction mechanisms of cotransmitter-mediated VC are more affected by age; however, it is clear that postsynaptic VC function mediated by both NPY and ATP, the two most likely sympathetic cotransmitters, is reduced with age.
After complete antagonism of both -and ß-adrenoceptors, thus eliminating any contribution of NA to the reflex VC response during cooling, no VC was observed in the older subjects, leading to the conclusion that the only functional neurotransmitter contributing to VC in aged human skin is NA. Because cotransmitters contributed to 37% of the VC response in young subjects, yet ageing induced a total loss of 54% of the VC response, there was a smaller portion of this loss not accounted for by the lack of functional cotransmitters. Several studies have suggested that, as is the case in other vascular beds in the human body, the effects of NA may be blunted in aged skin (Nielsen et al. 1992; Frank et al. 1996, 2000). Although there was no age difference in VC after the first 5 min of NA infusion (see Fig. 2), attenuated VC in older subjects after the full 10 min NA infusion (see Fig. 3) suggests that NA function may be compromised in aged human skin and may account for the remaining loss of VC associated with ageing. If, as is suggested by the present study, NA is the only functional transmitter in the VC response to cooling, and NA-mediated VC is blunted with ageing, then the combination of these two neurovascular phenomena which limit the capacity of vessels to constrict in response to cold may predispose the elderly to hypothermia. Indeed, Collins et al. (1977), Budd et al. (1991), and Inoue et al. (1992) suggest that older humans are at a higher risk for excessive heat loss, leading to hypothermia. The findings of the present study set forth a plausible theory as to the mechanistic events underlying this age-associated problem.
NA infusion
During the 10 min infusion of NA at all sites, no VC occurred at the Y + P site in either young or older subjects; attenuated VC (compared to control) was observed at the BT site in young subjects, whereas no VC occurred at the BT site in older subjects. These observations highlight three important points. First, the lack of any VC response at the Y + P site during NA infusion, especially during the first 5 min, indicates that the adrenoceptor block was fully intact in the presence of NA; therefore, any reduction in CVC observed at the Y + P site during cooling can confidently be attributed to non-NA mediators. During the last 5 min of NA infusion, there was a non-significant tendency (P= 0.38) to VC at the Y + P site in young subjects. This may be attributed to the relatively high concentration of NA (100 µM) that was infused, which most likely began to overwhelm the competitive Y + P block towards the end of the infusion protocol.
Second, attenuated VC observed in young subjects at the BT site during NA infusion indicates that the effects of NA are altered at sites pre-treated with this antagonist when compared to untreated sites. BT is a selective presynaptic adrenergic antagonist and should not exert any effects on postsynaptic adrenoceptors. Yet the attenuated VC observed at the BT site indicates that this drug may interfere with the ability of NA to fully stimulate VC via postsynaptic adrenoceptors. This may be due to its mechanism of action; when BT binds presynaptically, it induces a release of the axon terminal's contents into the synaptic cleft. The sudden release of high quantities of NA from the axon may have been sufficient to acutely desensitize -adrenoceptors (Carrier et al. 1978; Lurie et al. 1985).
Finally, the age-related alteration in VC patterns at the BT site (age x site x time interaction: P= 0.0003) suggests that BT may affect receptors differently in older subjects. Specifically, adrenoceptors may have recovered from acute desensitization more quickly in young subjects, accounting for the partial VC observed in the young group compared to the marked lack of VC observed in the older group.
Summary
The present study presents evidence that reflex cutaneous VC in response to whole-body cooling in young humans comprises both NA-mediated and cotransmitter-mediated portions, in agreement with Stephens et al. (2001, 2002a). In contrast, older subjects exhibit significantly attenuated VC in response to cooling, and this compromised response is largely due to the fact that non-NA-mediated mechanisms do not contribute to reflex cutaneous VC as humans age. This loss of cotransmitter function may be due to changes in transmitter synthesis, receptor number, or postreceptor second-messenger function. Conclusions from the present study help clarify the mechanisms underlying age-related impairments in VC capacity that may predispose older humans to excessive heat loss and subsequent hypothermia.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Bradley E, Law A, Bell D & Johnson CD (2003). Effects of varying impulse number on cotransmitter contributions to sympathetic vasoconstriction in rat tail artery. Am J Physiol 284, H2007–H2014.
Budd GM, Brotherhood JR, Hendrie AL & Jeffery SE (1991). Effects of fitness, fatness, and age on men's responses to whole body cooling in air. J Appl Physiol 71, 2387–2393.
Burnstock G (1999). Purinergic cotransmission. Brain Res Bull 50, 355–357.[CrossRef][Medline]
Carrier O, Wedell EK & Barron KW (1978). Specific -adrenergic receptor desensitisation in vascular smooth muscle. Blood Vessels 15, 247–258.[Medline]
Collins KJ, Dore C, Exton-Smith AN, Fox RH, MacDonald IC & Woodward PM (1977). Accidental hypothermia and impaired temperature homeostasis in the elderly. Br Med J 1, 353–356.[Medline]
Connat JL, Busseuil D, Gambert S, Ody M, Tébaldini M, Gamboni S et al. (2001). Modification of the rat aortic wall during ageing; possible relation with decrease of peptidergic innervation. Anat Embryol 204, 455–468.[CrossRef][Medline]
Dhall U, Cowen T, Haven AJ & Burnstock G (1986). Perivascular noradrenergic and peptide-containing nerves show different patterns of changes during development and ageing in the guinea-pig. J Auton Nerv Sys 16, 109–126.[CrossRef][Medline]
Dinenno FA, Dietz NM & Joyner MJ (2002). Aging and forearm postjunctional -adrenergic vasoconstriction in healthy men. Circulation 106, 1349–1354.
Ekblad E, Edvinsson L, Wahlestedt C, Uddman R, Håkanson R & Sundler F (1984). Neuropeptide Y co-exists and co-operates with noradrenaline in perivascular nerve fibers. Regul Pept 8, 225–235.[CrossRef][Medline]
Frank SM, El-Gamal N, Raja SN & Wu PK (1996). -Adrenoceptor mechanisms of thermoregulation during cold challenge in humans. Clin Sci 91, 627–631.[Medline]
Frank SM, Raja SN, Bulcao C & Goldstein DS (2000). Age-related thermoregulatory differences during core cooling in humans. Am J Physiol 279, R349–R354.
Fried G, Terenius L, Hökfelt T & Goldstein M (1985). Evidence for differential localization of noradrenaline and neuropeptide Y in neuronal storage vesicles isolated from rat vas deferens. J Neurosci 5, 450–458.[Abstract]
García-Villalón AL, Padilla J, Fernández N, Monge L, Martínez MA, Gómez B et al. (2000). Effect of neuropeptide Y on the sympathetic contraction of the rabbit central ear artery during cooling. Eur J Physiol 440, 548–555.[Medline]
Goldberg MR & Robertson D (1983). Yohimbine: a pharmacological probe for study of the alpha 2-adrenoreceptor. Pharmacol Rev 35, 143–180.[Medline]
Han S, Yang C, Chen X, Naes L, Cox BF & Westfall T (1998). Direct evidence for the role of neuropeptide Y in sympathetic nerve stimulation-induced vasoconstriction. Am J Physiol 274, H290–H294.[Medline]
Hogikyan RV & Supiano MA (1994). Arterial -adrenergic responsiveness is decreased and SNS activity is increased in older humans. Am J Physiol 266, E717–E724.[Medline]
Inoue Y, Nakao M, Araki T & Ueda H (1992). Thermoregulatory responses of young and older men to cold exposure. Eur J Appl Physiol 65, 492–498.[CrossRef]
Kenney WL & Armstrong CG (1996). Reflex peripheral vasoconstriction is diminished in older men. J Appl Physiol 80, 512–515.
Khan F, Spence VA & Belch JJF (1992). Cutaneous vascular responses and thermoregulation in relation to age. Clin Sci 82, 521–528.[Medline]
Konishi C, Naito Y & Ohara N (1999). Age-related changes in adenosine 5'-triphosphate-induced constriction of isolated, perfused mesenteric arteries in rats. Life Sci 64, 1265–1273.[CrossRef][Medline]
Lambert ML, Callow ID, Feng Q & Arnold JMO (1999). The effects of age on human venous responsiveness to neuropeptide Y. Br J Clin Pharmacol 47, 83–89.[CrossRef][Medline]
Landsberg L (1994). Introduction: increased sympathetic nervous system activity in the elderly. Br J Clin Pracsupplement 74, 1–3.
Lundberg JM (1996). Pharmacology of cotransmission in the autonomic nervous system: integrative aspects on amines, neuropeptides, adenosine triphosphate, amino acids, and nitric oxide. Pharmacol Rev 48, 113–178.[Medline]
Lundberg JM, Franco-Cereceda A, Hemsén A, Lacroix JS & Pernow J (1990). Pharmacology of noradrenaline and neuropeptide tyrosine (NPY)-mediated sympathetic cotransmission. Fundam Clin Pharmacol 4, 373–391.[Medline]
Lurie KG, Tsujimoto G & Hoffman BB (1985). Desensitization of alpha-1 adrenergic receptor-mediated vascular smooth muscle contraction. J Pharmacol Exp Ther 234, 147–152.
Morris JL (1999). Cotransmission from sympathetic vasoconstrictor neurons to small cutaneous arteries in vivo. Am J Physiol 277, H58–H64.[Medline]
Nielsen H, Hasenkam JM, Pilegaard HK, Aalkj?, RC & Mortensen FV (1992). Age-dependent changes in -adrenoceptor-mediated contractility of isolated human resistance arteries. Am J Physiol 263, H1190–H1196.[Medline]
Nilsson T, You J, Sun X, Hedner T & Edvinsson L (1996). Characterization of neuropeptide Y receptors mediating contraction, potentiation and inhibition of relaxation. Blood Pressure 5, 164–169.[Medline]
Racchi H, Irarrázabal MJ, Howard M, Morán S, Zalaquett R & Huidobro-Toro JP (1999). Adenosine 5'-triphosphate and neuropeptide Y are co-transmitters in conjunction with noradrenaline in the human saphenous vein. Br J Pharmacol 126, 1175–1185.[CrossRef][Medline]
Racchi H, Schliem AJ, Donoso MV, Rahmer A, Zúñiga A, Guzmán S et al. (1997). Neuropeptide Y Y1 receptors are involved in the vasoconstriction caused by human sympathetic nerve stimulation. Eur J Pharmacol 329, 79–83.[CrossRef][Medline]
Ralevic V & Burnstock G (1991). Roles of P2-purinoceptors in the cardiovascular system. Circulation 84, 1–14.
Richardson D, Tyra J & McCray A (1992). Attenuation of the cutaneous vasoconstrictor response to cold in elderly men. J Gerontol 47, M211–M214.[Medline]
Stachenfeld NS, Silva C & Keefe DL (2000). Estrogen modifies the temperature effects of progesterone. J Appl Physiol 88, 1643–1649.
Stephens DP, Aoki K, Kosiba WA & Johnson JM (2001). Nonnoradrenergic mechanism of reflex cutaneous vasoconstriction in men. Am J Physiol 280, H1496–H1504.
Stephens DP, Bennett LAT, Aoki K, Kosiba WA, Charkoudian N & Johnson JM (2002a). Sympathetic nonnoradrenergic cutaneous vasoconstriction in women is associated with reproductive hormone status. Am J Physiol 282, H264–H272.
Stephens DP, Saad AR, Bennett LAT & Johnson JM (2002b). Neuropeptide Y participates in reflex cutaneous vasoconstriction. FASEB J 16, A81–A82 (Abstract).
Taddei S, Pedrinelli R & Salvetti A (1990). Sympathetic nervous system-dependent vasoconstriction in humans: evidence for mechanistic role of endogenous purine compounds. Circulation 82, 2061–2067.
Wahlestedt C, Håkanson R, Vaz CA & Zukowska-Grojec Z (1990). Norepinephrine and neuropeptide Y: vasoconstrictor cooperation in vivo and in vitro. Am J Physiol 258, R736–R742.[Medline]
|
Acknowledgements |
|---|
This article has been cited by other articles:
|
|
 |
|
  C. S. Thompson-Torgerson, L. A. Holowatz, N. A. Flavahan, and W. Larry Kenney Rho kinase-mediated local cold-induced cutaneous vasoconstriction is augmented in aged human skin Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H30 - H36. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Burnstock Physiology and Pathophysiology of Purinergic Neurotransmission Physiol Rev, April 1, 2007; 87(2): 659 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Thompson-Torgerson, L. A. Holowatz, N. A. Flavahan, and W. L. Kenney Cold-induced cutaneous vasoconstriction is mediated by Rho kinase in vivo in human skin Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1700 - H1705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. W. DeGroot and W. L. Kenney Impaired defense of core temperature in aged humans during mild cold stress Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R103 - R108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. A. Kluess, J. B. Buckwalter, J. J. Hamann, D. S. DeLorey, and P. S. Clifford Frequency and pattern dependence of adrenergic and purinergic vasoconstriction in rat skeletal muscle arteries Exp Physiol, November 1, 2006; 91(6): 1051 - 1058. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. G. Helwig, S. Parimi, C. K. Ganta, R. Cober, R. J. Fels, and M. J. Kenney Aging alters regulation of visceral sympathetic nerve responses to acute hypothermia Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2006; 291(3): R573 - R579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Kellogg Jr In vivo mechanisms of cutaneous vasodilation and vasoconstriction in humans during thermoregulatory challenges J Appl Physiol, May 1, 2006; 100(5): 1709 - 1718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Thompson, L. A. Holowatz, and W. L. Kenney Cutaneous vasoconstrictor responses to norepinephrine are attenuated in older humans Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2005; 288(5): R1108 - R1113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S Thompson, L. A Holowatz, and W. L. Kenney Attenuated noradrenergic sensitivity during local cooling in aged human skin J. Physiol., April 1, 2005; 564(1): 313 - 319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. Wilson, K. D. Monahan, D. S. Short, and C. A. Ray Effect of age on cutaneous vasoconstrictor responses to norepinephrine in humans Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2004; 287(5): R1230 - R1234. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
P < 0.001 versus control; 
P < 0.001 versus young.
