HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Free All Versions of this Article: 95/6/2370    most recent 00634.2003v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Rosenmeier, J. B. Articles by Joyner, M. J. Search for Related Content PubMed PubMed Citation Articles by Rosenmeier, J. B. Articles by Joyner, M. J.

Exogenous NO administration and -adrenergic vasoconstriction in human limbs

Department of Anesthesiology and General Clinical Research Center, Mayo Clinic and Foundation, Rochester, Minnesota 55905

Submitted 18 June 2003 ; accepted in final form 11 August 2003

	ABSTRACT

TOP ABSTRACT METHODS RESULTS DISCUSSION DISCLOSURES REFERENCES

 
Nitric oxide (NO) is capable of blunting -adrenergic vasoconstriction in contracting skeletal muscles of experimental animals (functional sympatholysis). We therefore tested the hypothesis that exogenous NO administration can blunt -adrenergic vasoconstriction in resting human limbs by measuring forearm blood flow (FBF; Doppler ultrasound) and blood pressure in eight healthy males during brachial artery infusions of three -adrenergic constrictors (tyramine, which evokes endogenous norepinephrine release; phenylephrine, an ₁-agonist; and clonidine, an ₂-agonist). To simulate exercise hyperemia, the vasoconstriction caused by the -agonists was compared during adenosine-mediated (>50% NO independent) and sodium nitroprusside-mediated (SNP; NO donor) vasodilation of the forearm. Both adenosine and SNP increased FBF from 35–40 to 200–250 ml/min. All three -adrenergic constrictor drugs caused marked reductions in FBF and calculated forearm vascular conductance (P < 0.05). The relative reductions in forearm vascular conductance caused by the -adrenergic constrictors during SNP infusion were similar (tyramine, –74 ± 3 vs. –65 ± 2%; clonidine, –44 ± 6 vs. –44 ± 6%; P > 0.05) or slightly greater (phenylephrine, –47 ± 6 vs. –33 ± 6%; P < 0.05) compared with the responses during adenosine. In conclusion, these results indicate that exogenous NO sufficient to raise blood flow to levels simulating those seen during exercise does not blunt -adrenergic vasoconstriction in the resting human forearm.

functional sympatholysis; sympathetic nervous system; sympathetic modulation; nitric oxide

With this information as a background, we sought to determine whether -adrenergic vasoconstriction is blunted in resting skeletal muscle vasodilated with the NO donor SNP. We also determined whether postjunctional ₁- or ₂-adrenergic receptor-mediated vasoconstriction was affected. Our interest in this topic was also stimulated by recent findings from our laboratory demonstrating that sympatholysis is robust in humans, but the mechanisms responsible might differ from those identified in rodent muscle (15, 23). However, on the basis of animal studies we hypothesized that -adrenergic vasoconstriction in human muscle would be blunted by exogenous administration of NO and that ₂-mediated constriction would be blunted more than ₁-mediated constriction (8, 20, 22).

	METHODS

TOP ABSTRACT METHODS RESULTS DISCUSSION DISCLOSURES REFERENCES

 
After institutional review board approval and written, informed consent, eight healthy nonobese male subjects between 22 and 33 yr old participated in the study. The studies were performed at 20°C to minimize skin blood flow to the hand. Subjects had their forearm volume measured by using water displacement so that forearm drug infusions could be normalized according to forearm volume. Subjects were studied in the supine position with the nondominant arm extended laterally at heart level. After local anesthesia (1% lidocaine), a 5-cm 20-gauge catheter was inserted into the brachial artery by use of aseptic technique. A stopcock and port system permitted measurement of arterial pressure and infusion of study drugs into the same artery (4). Heart rate was measured with a 5-lead ECG.

Forearm blood flow. A pulsed Doppler probe (4 MHz, model 500 V, Multigon Industries) was used to measure brachial artery mean blood velocity (MBV). The probe was securely fixed to the skin 10 cm upstream from the catheter to minimize turbulence during the drug infusion. The probe insonation angle was 60°. A linear 7.0-MHz echo Doppler ultrasound probe (Acuson 128xp/10) was placed in a holder securely fixed to the skin 3 cm proximal from the velocity probe to measure brachial artery diameter. Forearm blood flow (FBF) was calculated as FBF = MBV x (brachial artery diameter/2)² x 60 (15, 23).

Vasoactive drug infusions. All infusions were performed at rest. We sought to match blood flow between two different vasodilator drug infusions by using adenosine (6.25 µg · dl forearm volume^–1 · min^–1) and SNP (0.5 µg · dl forearm volume^–1 · min^–1). The drug doses used in this study were based on previous studies demonstrating approximately four- to sixfold increases in limb blood flow, which are similar to the hyperemia observed during mild forearm handgripping (13, 15, 23). Adenosine (control dilator) evokes vasodilation that is >50% NO independent, whereas SNP (experimental dilator) is a NO donor (19).

The following drugs were also infused via the brachial artery catheter to evoke -adrenergic vasoconstriction. Tyramine was infused at 8 µg · dl forearm volume^–1 · min^–1 on the basis of the effects of forearm exercise on the tyramine vasoconstrictor dose-response curves reported by Tschakovsky et al. (23). Tyramine evokes norepinephrine (NE) "leakage" from neuronal vesicles and consequent diffusion of NE out of nerve terminals, thus resulting in stimulation of ₁- and ₂-adrenergic receptors (1). Phenylephrine (a selective ₁-agonist) was infused at 0.0312 µg · dl forearm volume^–1 · min^–1, and clonidine (an ₂-agonist) was infused at 0.15 µg · dl forearm volume^–1 · min^–1. The doses of phenylephrine and clonidine were based on our previous studies at rest and during handgripping (5, 15).

Experimental protocol. SNP and adenosine infusions lasted for 7 min. In each case, steady-state FBF was reached within 3 min. Between 3 and 4 min, the appropriate dose of -adrenergic agonist was calculated on the basis of forearm volume and blood flow, and the infusion began at the 4-min mark and lasted for 3 min (15, 23). The vasoconstrictor infusions were adjusted for the blood flow to ensure the same arterial concentrations across conditions. A 20-min break was allowed between each adenosine and SNP trial. SNP and adenosine infusions alternated. The order of the tyramine, phenylephrine, and clonidine infusions was randomized and counterbalanced across subjects. Blood flow comparisons were made between minute 3–4 of the vasodilator infusions and the final minute of combined vasodilator and -adrenergic vasoconstrictor infusions.

Data acquisition and analysis. Data were digitized and collected at 250 Hz and stored on computer to be analyzed by use of off-line Windaq processing software. Mean arterial pressure (MAP) was determined from the arterial pressure waveform.

Forearm vascular conductance (FVC) was calculated as

The % reduction in FVC was calculated as

We used percent reduction in FVC to compare vasoconstriction across conditions when blood flow and conductance might differ. After much discussion, this index has emerged as a standard way to compare interventions that alter vasomotor tone when baseline flow varies (2, 10, 23).

Statistics. All values are reported as means ± SE. Specific hypothesis testing within each of the exercise or adenosine trials with the three different drug infusions was performed by use of Student's paired t-test. Significance was set at P < 0.05.

	RESULTS

TOP ABSTRACT METHODS RESULTS DISCUSSION DISCLOSURES REFERENCES

 
Resting blood flows averaged 40 ml/min between all trials.

Tyramine infusion (₁- and ₂-stimulation). During adenosine (i.e., control) and SNP infusion, absolute FBF (210 ± 15 vs. 236 ± 29 ml/min) was not different between the two conditions. Similarly, FVC between the two conditions was not different (233 ± 18 vs. 286 ± 34 ml · min^–1 · 100 mmHg; Fig. 1). There was a drop (8 mmHg) in mean arterial pressure during SNP infusion, suggesting systemic effects of the drug. This was not the case for adenosine. During tyramine infusion there was a marked reduction in blood flow in both conditions to 52 ± 4 and 91 ± 16 ml/min for adenosine and SNP, respectively. However, the percent reduction in FVC during both adenosine infusion and SNP infusion was similar (–74 ± 3 and –65 ± 3%, respectively, P > 0.05).

View larger version (15K): [in this window] [in a new window]   Fig. 1. Effects of tyramine on adenosine- vs. nitroprusside-induced forearm vasodilation. Baseline forearm vascular conductance and the hyperemic responses to both adenosine and sodium nitroprusside (SNP) were similar. Tyramine caused a profound vasoconstriction during both vasodilator infusions, suggesting that nitric oxide (NO) does not modulate sympathetic vasoconstriction under these conditions. *P < 0.05 vs. hyperemic value within each condition.

Phenylephrine infusion (₁-stimulation). During adenosine and SNP infusion, absolute FBF (216 ± 21 vs. 239 ± 20 ml/min) and FVC (244 ± 25 vs. 283 ± 24 ml · min^–1 · 100 mmHg) were not different (Fig. 2). MAP fell from 89 ± 2 to 84 ± 2 mmHg during SNP infusion but remained unchanged throughout the adenosine infusion. Blood flows during phenylephrine infusion fell to 141 ± 14 ml/min during adenosine and to 125 ± 17 ml/min during SNP. Phenylephrine caused a significantly greater percent reduction in vascular conductance during SNP infusion than during adenosine (–47 ± 6 vs. –33 ± 6%, P < 0.05).

View larger version (15K): [in this window] [in a new window]   Fig. 2. Effects of phenylephrine on adenosine- vs. nitroprusside-induced forearm vasodilation. Baseline forearm vascular conductance and hyperemic responses to adenosine and SNP were similar. Phenylephrine infusion caused significant vasoconstriction in both conditions that was more pronounced during the SNP trial (P < 0.05), indicating that postjunctional 1-vasoconstriction is not affected by exogenous NO. *P < 0.05 vs. hyperemic value within each condition.

Clonidine infusion. During adenosine and SNP infusion, absolute FBF (191 ± 14 vs. 252 ± 32 ml/min) and FVC (210 ± 18 vs. 291 ± 38 ml · min^–1 · 100 mmHg) were not different (Fig. 3). MAP fell from 93 ± 2to87 ± 2 mmHg during SNP infusion but remained unchanged with adenosine. Blood flows during clonidine infusion fell to 106 ± 12 ml/min during adenosine and to 142 ± 25 ml/min during SNP. Clonidine caused an equal percent reduction in vascular conductance during both adenosine and SNP infusion (–44 ± 6 and –44 ± 6%, respectively).

View larger version (15K): [in this window] [in a new window]   Fig. 3. Effects of clonidine on adenosine- vs. nitroprusside-induced forearm vasodilation. Baseline forearm vascular conductance and hyperemic responses during both infusions were similar. Clonidine caused profound vasoconstriction in both conditions, indicating that postjunctional 2-adrenergic vasoconstriction is not affected by exogenous NO. *P < 0.05 vs. hyperemic value within each condition.

	DISCUSSION

TOP ABSTRACT METHODS RESULTS DISCUSSION DISCLOSURES REFERENCES

 
The main finding of the present study is that both ₁- and ₂-adrenergic receptor-mediated vasoconstriction remained intact in resting human skeletal muscle vasodilated with the NO donor SNP. Our findings contrast with data from the key animal study, in which NO clearly contributes to functional sympatholysis and causes diminished sensitivity to ₂-adrenergic but not ₁-receptor-mediated vasoconstriction (22). In other animal studies, both ₁- and ₂-vasoconstriction are blunted during contractions, but ₂-mediated constriction is blunted more noticeably (2, 12).

It has also been shown that the ability of skeletal muscle contraction to blunt -adrenoreceptor activation is impaired in nNOS-deficient skeletal muscle both in mdx mice (an animal model of Duchenne muscular dystrophy in which the activity and expression of nNOS are greatly reduced) and in nNOS knockout mice (21). These findings have been supported in humans with Duchenne muscular dystrophy by using near infrared spectroscopy as an indirect measurement of blood flow (16). Together, these data suggest a specific antagonistic interaction between NO and -adrenergic vasoconstriction in active skeletal muscle. Endogenous NO also attenuates sympathetic constriction in the rat intestinal microvasculature (11). One possible site of interaction appears to be at the level of the vascular smooth muscle regulatory light chain, where SNP inhibits -receptor-mediated phosphorylation (8). However, in our study there was no diminished sensitivity to -adrenergic vasoconstriction evoked by either ₁- or ₂-receptor agonists despite substantial doses of exogenous NO.

Along similar lines was a study by Engelke et al. (6), who infused both SNP and acetylcholine (endothelium-dependent NO release) separately into the forearm. In this study lower body negative pressure (LBNP) was used to increase sympathetic nervous activity and evoke -adrenergic vasoconstriction. The effects of the LBNP on the blood flow responses to SNP indicated that sympathetic activity could modulate NO-mediated vasodilation, suggesting that NO did not have any sympatholytic effects in the resting human forearm. These data also challenge the proposition that NO might oppose -adrenergic vasoconstriction by inhibition of NE release at the sympathetic varicosities (3, 9). However, in the present study we used tyramine to evoke NE release as opposed to LBNP and although the source of the NE release is similar, the mechanisms evoking NE release differ (1). Therefore we cannot draw definitive conclusions about the effects of NO on NE release.

NO and adenosine have both been suggested as key metabolites causing functional sympatholysis. In a previous study, we clearly demonstrated no sympatholytic effects of adenosine (15, 23). Additionally, in this study the only differences observed during infusion of either adenosine or SNP were with phenylephrine, which caused a greater percent reduction in FVC during SNP (–47%) than with adenosine (–33%) infusion. A similar finding was made by Smits et al. (18), who used tyramine, NE, and LBNP to stimulate sympathetic activity during adenosine vs. SNP infusion in resting human forearms and demonstrated a larger percent increase in vascular resistance to both tyramine and NE during SNP than during adenosine infusion. These observations led them to conclude that adenosine might be an important endogenous modulator of sympathetic nervous activity. However, it was later shown that adenosine does not affect the blunting of sympathetic vasoconstriction during exercise (22).

The present study also differs from that of Smits et al. (18) in that we used doses of the vasodilator drugs designed to evoke increases in blood flow compatible with those seen during handgrip exercise (15, 23). In this study we used two different high-blood-flow states to simulate exercise hyperemia. The SNP blood flow values closely matched the blood flow levels seen during mild exercise in our previous studies (15, 23) in which we used adenosine as a high-flow control to demonstrate that it is exercise rather than high blood flow alone that causes the attenuation of sympathetic constriction in contracting muscle. This approach also minimizes any analytical confusion associated with comparing vasoconstrictor responses between resting and hyperemic conditions (2, 10, 23).

There are several limitations to the present study. First, SNP tended to cause more vasodilation than adenosine. This might cloud some of the detailed comparisons of adrenergic vasoconstriction when differing dilators (adenosine vs. SNP) were used. However, this possibility should not detract from our finding that marked adrenergic vasoconstriction continued to occur in limbs passively dilated with drugs. This observation contrasts markedly with the observations made during exercise with the use of identical approaches (15, 23). Second, we gave SNP via a brachial catheter to deliver NO to the forearm. This route of delivery is clearly different from how NO from either eNOS or nNOS would reach the vascular smooth muscle during contractions. However, our approach was conceptually similar to the study of Grange et al. (8) in isolated rodent blood vessels, which showed that exogenous NO administration blunts sympathetic vasoconstriction in vitro. By contrast, VanTeeffelen and Segal (24) performed studies in the hamster retractor muscle and found that SNP had little effect on the constrictor responses evoked by sympathetic nerve stimulation. Given the differences in these two animal studies and the previous studies in rodents, we cannot rule out the possibility that effects of exogenous NO administration on sympathetic vasoconstriction differ from the effects of NO generated during contractions (8, 20–22, 24).

In summary, we have demonstrated that large amounts of exogenous NO are unable to attenuate either ₁- or ₂-vasoconstrictor responsiveness in the resting human forearm. These data question the role of NO during functional sympatholysis in humans. Our study was not performed during muscle contraction, so absolute comparisons to exercise are not possible with the present data. However, when the present data are viewed in the context of previous studies (15, 23), our approach and conclusions that NO is not obligatory for functional sympatholysis in humans seem reasonable. These conclusions are further strengthened because NO seems to play a limited role in human exercise hyperemia (7, 17).

	DISCLOSURES

TOP ABSTRACT METHODS RESULTS DISCUSSION DISCLOSURES REFERENCES

 
J. B. Rosenmeier was a visiting fellow from the Copenhagen Muscle Research Centre, and her research was supported by the Danish Heart Foundation Grant 136022812, Astra Zeneca, Novo Nordisk Foundation, The Fulbright Commission, Denmark. This study was also supported by the National Institutes of Health (NIH) Grants HL-46493 and NS-32353 to M. J. Joyner; by NIH Grant F32 AG-05912 to F. A. Dinenno; and by NIH General Clinical Research Center Grant RR-00585 (Mayo Clinic).

	FOOTNOTES

 

Address for reprint requests and other correspondence: M. J. Joyner, Dept. of Anesthesiology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905 (E-mail: joyner.michael{at}mayo.edu).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

	REFERENCES

TOP ABSTRACT METHODS RESULTS DISCUSSION DISCLOSURES REFERENCES

 

1. Brandao F, Rodrigues-Pereira E, Guilherme Monteiro J, and Osswald W. Characteristics of tyramine induced release of noradrenaline: mode of action of tyramine and metabolic fate of the transmitter. Naunyn Schmiedebergs Arch Pharmacol 311: 9–15, 1980.[Web of Science][Medline]
2. Buckwalter JB, Naik JS, Valic Z, and Clifford PS. Exercise attenuates -adrenergic-receptor responsiveness in skeletal muscle vasculature. J Appl Physiol 90: 172–178, 2001.[Abstract/Free Full Text]
3. Cohen RA and Weisbrod RM. Endothelium inhibits norepinephrine release from adrenergic nerves of rabbit carotid artery. Am J Physiol Heart Circ Physiol 254: H871–H878, 1988.[Abstract/Free Full Text]
4. Dietz NM, Rivera JM, Eggener SE, Fix RT, Warner DO, and Joyner MJ. Nitric oxide contributes to the rise in forearm blood flow during mental stress in humans. J Physiol 480: 361–368, 1994.[Abstract/Free Full Text]
5. Dinenno FA, Dietz NM, and Joyner MJ. Aging and forearm post-junctional -adrenergic vasoconstriction in healthy men. Circulation 106: 1349–1354, 2002.[Abstract/Free Full Text]
6. Engelke KA, Williams MM, Dietz NM, and Joyner MJ. Does sympathetic activation blunt nitric oxide-mediated hyperemia in the human forearm? Clin Auton Res 7: 85–91, 1997.[Web of Science][Medline]
7. Frandsenn U, Bangsbo J, Sander M, Hoffner L, Betak A, Saltin B, and Hellsten Y. Exercise-induced hyperaemia and leg oxygen uptake are not altered during effective inhibition of nitric oxide synthase with N^G-nitro-L-arginine methyl ester in humans. J Physiol 15: 257–264, 2001.
8. Grange RW, Isotani E, Lau KS, Kamm KE, Huang PL, and Stull JT. Nitric oxide contributes to vascular smooth muscle relaxation in contracting fast-twitch muscles. Physiol Genomics 5: 35–44, 2001.[Abstract/Free Full Text]
9. Greenberg SS, Diecke FP, Peevy K, and Tanaka TP. Release of norepinephrine from adrenergic nerve endings of blood vessels is modulated by endothelium-derived relaxing factor. Am J Hypertens 3: 211–218, 1990.[Web of Science][Medline]
10. Lautt WW. Resistance or conductance for expression of arterial vascular tone. Microvasc Res 37: 230–236, 1989.[Web of Science][Medline]
11. Nase GP and Boegehold MA. Nitric oxide modulates arteriolar responses to increased sympathetic nerve activity. Am J Physiol Heart Circ Physiol 271: H860–H869, 1996.[Abstract/Free Full Text]
12. Ohyanagi M, Faber JE, and Nishigaki K. Differential activation of alpha 1- and alpha 2-adrenoceptors on microvascular smooth muscle during sympathetic nerve stimulation. Circ Res 68: 232–244, 1991.[Abstract/Free Full Text]
13. Radegran G and Calbet JA. Role of adenosine in exercise-induced human skeletal muscle vasodilatation. Acta Physiol Scand 171: 177–185, 2001.[Web of Science][Medline]
14. Remensnyder JP, Mitchell JH, and Sarnoff SJ. Functional sympatholysis during muscular activity. Circ Res 11: 370–380, 1962.[Abstract/Free Full Text]
15. Rosenmeier JB, Dinenno FA, Fritzlar SJ, and Joyner MJ. ₁- and ₂-adrenergic vasoconstriction is blunted in contracting human muscle. J Physiol 547: 971–976, 2003.[Abstract/Free Full Text]
16. Sander M, Chavoshan B, Harris SA, Iannaccone ST, Stull JT, Thomas GD, and Victor RG. Functional muscle ischemia in neuronal nitric oxide synthase-deficient skeletal muscle of children with Duchenne muscular dystrophy. Proc Natl Acad Sci USA 97: 13818–13823, 2000.[Abstract/Free Full Text]
17. Shoemaker JK, Halliwill JR, Hughson RL, and Joyner MJ. Contributions of acetylcholine and nitric oxide to forearm blood flow at exercise onset and recovery. Am J Physiol Heart Circ Physiol 273: H2388–H2395, 1997.[Abstract/Free Full Text]
18. Smits P, Lenders JW, Willemsen JJ, and Thien T. Adenosine attenuates the response to sympathetic stimuli in humans. Hypertension 18: 216–223, 1991.[Abstract/Free Full Text]
19. Smits P, Williams SB, Lipson DE, Banitt P, Rongen GA, and Creager MA. Endothelial release of nitric oxide contributes to the vasodilator effect of adenosine in humans. Circulation 92: 2135–2141, 1995.[Abstract/Free Full Text]
20. Thomas GD, Hansen J, and Victor RG. Inhibition of ₂-adrenergic vasoconstriction during contraction of glycolytic, not oxidative, rat hindlimb muscle. Am J Physiol Heart Circ Physiol 266: H920–H929, 1994.[Abstract/Free Full Text]
21. Thomas GD, Sander M, Lau KS, Huang PL, Stull JT, and Victor RG. Impaired metabolic modulation of -adrenergic vasoconstriction in dystrophin-deficient skeletal muscle. Proc Natl Acad Sci USA 95: 15090–15095, 1998.[Abstract/Free Full Text]
22. Thomas GD and Victor RG. Nitric oxide mediates contraction-induced attenuation of sympathetic vasoconstriction in rat skeletal muscle. J Physiol 506: 817–826, 1998.[Abstract/Free Full Text]
23. Tschakovsky ME, Sujirattanawimol K, Ruble SB, Valic Z, and Joyner MJ. Is sympathetic neural vasoconstriction blunted in the vascular bed of exercising human muscle? J Physiol 541: 623–635, 2002.[Abstract/Free Full Text]
24. VanTeeffelen JW and Segal SS. Interaction between sympathetic nerve activation and muscle fibre contraction in resistance vessels of hamster retractor muscle. J Physiol 550: 563–574, 2003.[Abstract/Free Full Text]

This article has been cited by other articles:

				M. Shibasaki, P. Rasmussen, N. H. Secher, and C. G. Crandall Neural and non-neural control of skin blood flow during isometric handgrip exercise in the heat stressed human J. Physiol., May 1, 2009; 587(9): 2101 - 2107. [Abstract] [Full Text] [PDF]

				J. B. Rosenmeier, G. G. Yegutkin, and J. Gonzalez-Alonso Activation of ATP/UTP-selective receptors increases blood flow and blunts sympathetic vasoconstriction in human skeletal muscle J. Physiol., October 15, 2008; 586(20): 4993 - 5002. [Abstract] [Full Text] [PDF]

				B. S. Kirby, W. F. Voyles, R. E. Carlson, and F. A. Dinenno Graded sympatholytic effect of exogenous ATP on postjunctional {alpha}-adrenergic vasoconstriction in the human forearm: implications for vascular control in contracting muscle J. Physiol., September 1, 2008; 586(17): 4305 - 4316. [Abstract] [Full Text] [PDF]

				D. S. Goldstein Genotype and Vascular Phenotype Linked by Catecholamine Systems Circulation, January 29, 2008; 117(4): 458 - 461. [Full Text] [PDF]

				P. J Fadel, Z. Wang, H. Watanabe, D. Arbique, W. Vongpatanasin, and G. D Thomas Augmented sympathetic vasoconstriction in exercising forearms of postmenopausal women is reversed by oestrogen therapy J. Physiol., December 15, 2004; 561(3): 893 - 901. [Abstract] [Full Text] [PDF]

				G. D. Thomas and S. S. Segal Neural control of muscle blood flow during exercise J Appl Physiol, August 1, 2004; 97(2): 731 - 738. [Abstract] [Full Text] [PDF]

				L. B. Rowell Ideas about control of skeletal and cardiac muscle blood flow (1876-2003): cycles of revision and new vision J Appl Physiol, July 1, 2004; 97(1): 384 - 392. [Abstract] [Full Text] [PDF]

				J. B. Rosenmeier, J. Hansen, and J. Gonzalez-Alonso Circulating ATP-induced vasodilatation overrides sympathetic vasoconstrictor activity in human skeletal muscle J. Physiol., July 1, 2004; 558(1): 351 - 365. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Free All Versions of this Article: 95/6/2370    most recent 00634.2003v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Rosenmeier, J. B. Articles by Joyner, M. J. Search for Related Content PubMed PubMed Citation Articles by Rosenmeier, J. B. Articles by Joyner, M. J.