| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Other Original Studies |
Clinical Research Center, Franz Volhard Clinic, Max Delbrück Center, Medical Faculty of the Charité, Humboldt University (J.J., J.T., M.S., G.F., F.C.L.), 13125 Berlin, Germany; German Institute of Human Nutrition (M.B.), 14558 Potsdam, Germany; and Department of Internal Medicine and Endocrinology, Herlev Hospital, University of Copenhagen (N.J.C.), 2730 Copenhagen, Denmark
Address all correspondence and requests for reprints to: Jens Jordan, M.D., Clinical Research Center, Franz Volhard Clinic, Humboldt University, Wiltbergstrasse 50, 13125 Berlin, Germany.
Abstract
Nitric oxide (NO) may be an important modulator of sympathetic tone. We used im and sc microdialysis in humans to characterize the interaction of NO synthase inhibition and adrenoreceptor stimulation on tissue perfusion, metabolism, and norepinephrine release. Microdialysis probes were perfused with L- or D-nitro-L-arginine-methyl-ester (100 µmol/L) followed by incremental doses of isoproterenol, epinephrine, or nitroprusside. Blood flow was estimated based on the ethanol dilution technique. In muscle, the increase in blood flow with isoproterenol was abolished by L-NAME. The ethanol ratio was 0.03 ± 0.011 with D-NAME and 0.075 ± 0.014 with L-NAME during isoproterenol treatment (1 µmol/L). The effect was less pronounced in adipose tissue. The vasodilatory effect of nitroprusside was similar with D- and L-NAME. L-NAME augmented isoproterenol- and epinephrine-induced glycerol release. Dialysate glycerol during 1 µmol/L isoproterenol was 47 ± 6.7 µmol/L with D-NAME and 72 ± 15 µmol/L with L-NAME. In skeletal muscle, dialysate norepinephrine during 1 µmol/L isoproterenol treatment was 0.73 ± 0.17 and 1.3 ± 0.15 nmol/L with D- and L-NAME, respectively. We conclude that NO synthase inhibition attenuates ß2-adrenoreceptor-mediated vasodilation and enhances ß-adrenoreceptor-mediated lipolysis. These effects are in part mediated through an increase in interstitial norepinephrine concentrations. The data are consistent with the idea that in humans, NO is important in modulating and ameliorating sympathetic effects in peripheral tissues.
IMPAIRED NITRIC oxide (NO) production and
abnormalities in sympathetic nervous system function contribute to the
initiation and propagation of cardiovascular disease. Recent studies
suggest that these pathways are intimately related (1, 2).
For example, blockade of vascular 
-adrenoreceptors attenuates the
pressor effect of systemic NO synthase (NOS) inhibition in humans
(3). This observation is consistent with a tonic
inhibitory effect of NO on the sympathetic nervous system. The exact
site of the interaction is imperfectly understood in humans, but is
likely to occur in the central nervous system and the periphery. In
animals, central NOS inhibition is associated with an increase in
sympathetic nerve traffic and in blood pressure through interaction
with central baroreflex mechanisms (4, 5). A similar
NO-related central effect in humans is suggested by the observation
that the pressor response to NOS inhibition is associated with a
smaller than expected baroreflex-mediated decrease in sympathetic
traffic (6). In the periphery, NO may modulate sympathetic
effects through attenuation of norepinephrine release from
postganglionic sympathetic neurons (7) and through
interaction with adrenergic receptor mechanisms (8, 9).
For instance, ß2-adrenergic receptor-
mediated vasodilation in the forearm is blunted by NOS inhibition
(8). Given these interactions between sympathetic function
and NO, changes in NO production could lead to imbalance between
pressor and depressor mechanisms, particularly in response to
sympathetic stimuli. However, the effect of NO on norepinephrine
release from sympathetic neurons and its interaction with adrenergic
receptor stimulation are incompletely understood in humans. Whether NO
has a differential effect on adrenergic mechanisms in adipose tissue
and skeletal muscle, which are important for fuel storage and
utilization, is unknown. We used im and sc microdialysis
(10) in humans to test the hypothesis that NO modulates
the response to adrenergic receptor stimulation. We also characterized
the effect of NOS inhibition on norepinephrine release from
postganglionic adrenergic neurons.
Subjects and Methods
Subjects
Eight men closely matched for age (26 ± 2 yr), height (1.86 ± 0.09 m), and body mass (78 ± 11 kg) were included. All subjects were healthy, as determined by medical history, physical examination, and routine blood and urine tests. The subjects took no medications. The institutional review board approved all studies, and written informed consent was obtained. At least 24 h before the study, the subjects ingested a diet free of substances that could interfere with catecholamine measurements.
Microdialysis
After an overnight fast, two microdialysis catheters each were inserted into sc adipose tissue at the level of the umbilicus and into skeletal muscle (vastus lateralis muscle). Before insertion of the catheters, the respective areas were anesthetized with either EMLA creme (Astra USA, Inc., Wedel, Germany) for adipose tissue catheterization or sc injection of 1% lidocaine without epinephrine (Astra USA, Inc.) for muscle catheterization. After insertion of the probes, the perfusion was started at a flow rate of 2 µL/min with Ringer’s solution (Serumwerke Bernburg AG, Bernburg, Germany) supplemented with 50 mmol/L ethanol (for monitoring changes in blood flow) and 280 µmol/L ascorbate to prevent autooxidation of catecholamines). CMA/60 microdialysis catheters and CMA/102 microdialysis pumps (both from CMA Microdialysis AB, Solna, Sweden) were used.
Protocol
All studies were conducted at the Clinical Research Center. We conducted a series of separate microdialysis experiments. In an initial study we used im microdialysis to characterize the local effect of isoproterenol before and after systemic ß-blockade. In subsequent studies we tested the effects of isoproterenol (n = 8), epinephrine (n = 6), and sodium nitroprusside (n = 6) on tissue perfusion and metabolism, with and without NOS inhibition. We also studied the effect of NO inhibition on isoproterenol-induced norepinephrine release. NO formation from arginine by NOS was inhibited using the L-arginine analog N-nitro-L-arginine-methyl-ester (L-NAME). N-Nitro-D-arginine-methyl-ester (D-NAME) is the enantiomer of L-NAME, which does not inhibit NOS and served as the control compound.
Isoproterenol sensitivity and systemic ß-blockade
After a baseline period of 60 min, one probe was perfused with 0.01, 0.1, and 1.0 µmol/L isoproterenol (Abbot, Ottignies, France). The other probe was perfused with Ringer’s solution only. Then both probes were perfused with Ringer’s solution for 60 min. During the recovery period, systemic ß-blockade was achieved with four bolus doses of propranolol (0.05 mg/kg each). Continuous propranolol infusion at a rate of 0.033 mg/kg·h maintained ß-blockade through the remainder of the experiment. During ß-blockade, the two microdialysis probes were perfused just as before ß-blockade. Each perfusion step was maintained for 60 min. Samples were collected at 20-min intervals. Heart rate was determined by electrocardiogram, and blood pressure was determined by an automated oscillometric blood pressure cuff (Dinamap, Critikon, Tampa, FL).
Isoproterenol sensitivity and NOS inhibition
Two microdialysis probes were placed into adipose tissue, and two probes were placed im. After a baseline period of 45 min, either 100 µM L-NAME or D-NAME (CLINALFA, Laufelfingen, Switzerland) was added to the perfusion medium followed by incremental concentrations of isoproterenol (0.01, 0.1, and 1 µmol/L). In a subgroup of subjects, 10 µmol/L isoproterenol was also used. Each perfusion step was maintained for 45 min. Samples were collected at 15-min intervals.
Epinephrine sensitivity and NOS inhibition
Two sc and two im microdialysis probes were used. After a baseline period of 45 min, either 100 µmol/L L- or D-NAME was added to the perfusion medium, followed by incremental concentrations of epinephrine (0.01, 0.1, and 1 µmol/L; Suprarenin, Hoechst AG, Frankfurt, Germany). Each perfusion step was maintained for 45 min. Samples were collected at 15-min intervals.
Nitroprusside sensitivity and NOS inhibition
Two sc and two im microdialysis probes were used. After a baseline period of 45 min, probes were perfused with incremental concentrations of nitroprusside (0.43 and 4.3 mml/L; Nipruss, Schwarz-Pharma, Germany) and L-NAME or D-NAME, respectively. All dialysate samples were frozen at -80 C until analyses were performed.
Analyses
Changes in blood flow were determined using the ethanol dilution technique, which is based on Fick’s principle (11, 12, 13). The ethanol concentration was determined in the perfusate (inflow) and dialysate (outflow) using a standard enzymatic assay (14). A decrease in the ethanol concentration in the dialysate/ethanol concentration in the perfusate ratio is equivalent to an increase in blood flow and vice versa. For simplicity, the term ethanol ratio is substituted for ethanol concentration in the dialysate/ethanol concentration in perfusate ratio. Dialysate glycerol concentration was determined using an automated luminometric assay (15, 16); this measure was used for assessing changes in lipolysis and/or lipid mobilization (17). Concentrations of dialysate glucose and lactate were determined using the CMA/600 analyzer (CMA Microdialysis AB, Solna, Sweden). In situ recovery of the metabolites measured in the dialysate was about 30% for glycerol, glucose, and lactate using near-equilibrium dialysis at 0.3 µL/min (18). Samples for norepinephrine and epinephrine determinations were processed as previously described (19). Briefly, dialysate samples were collected in ice-cooled tubes containing ethylene glycol-bis-(ß-aminoethyl ether)-N,N,N',N'-tetraacetic acid), reduced glutathione, and 20 µL 6% albumin and were stored at -80 C until analyzed. The samples were freeze-dried before analysis; thereafter, 100 µL 6% albumin were added. Samples were precipitated with an equal volume of 0.6 N perchloric acid, and 100 µL supernatant were used. Appropriate blanks and standards were included. Norepinephrine was analyzed by a radioenzymatic method. The 3H-labeled derivative normetanephrine was isolated by high pressure liquid chromatography. The sensitivity of the assay was 0.5 pg.
Statistics
All data are expressed as the mean ± SEM. Intraindividual differences were compared by paired t tests. ANOVA testing for repeated measures was used for multiple comparisons (e.g. dose-response curves). P < 0.05 was considered statistically significant.
Results
Isoproterenol sensitivity and systemic ß-blockade
Figure 1
shows blood pressure and
heart rate with propranolol bolus application. Blood pressure was
120 ± 3.9/64 ± 3.4 mm Hg at baseline and 122 ±
3.7/65 ± 5.2 mm Hg during blockade (P = NS).
Heart rate decreased from 65 ± 3.3 beats/min at baseline to
54 ± 1.0 beats/min during blockade (P < 0.01;
Fig. 1, top). Isoproterenol applied through the
microdialysis catheter caused a dose-dependent increase in dialysate
glycerol concentration in the absence of systemic ß-blockade. The
dialysate glycerol concentration was 55 ± 5.5 µmol/L at
baseline and increased to 87 ± 4.1 µmol/L with 1 µmol/L
isoproterenol (P < 0.01). This response was abolished
by systemic ß-blockade. During blockade, the dialysate glycerol
concentration was 52 ± 4.2 µmol/L at baseline and 51 ±
2.4 µmol/L with 1 µmol/L isoproterenol.
|
The ethanol ratio was 0.21 ± 0.025 in adipose tissue and
0.06 ± 0.014 in skeletal muscle and did not change significantly
with L-NAME or D-NAME. Changes in ethanol ratio
with incremental concentrations of isoproterenol during
L-NAME or D-NAME are illustrated in Fig. 2 (top). In skeletal muscle,
the ethanol ratio was 0.07 ± 0.016 without isoproterenol and
0.03 ± 0.011 with 1 µmol/L isoproterenol in the presence of
D-NAME (P < 0.01). This marked
change was abolished by L-NAME (P
< 0.01, by ANOVA). In adipose tissue, isoproterenol decreased the
ethanol ratio from 0.20 ± 0.026 at baseline to 0.12 ± 0.024
with D-NAME (P = 0.01). The
ethanol ratio was greater during L-NAME than
during D-NAME (P < 0.05).
|
, middle). During 1 µmol/L isoproterenol, the dialysate
glycerol concentration was 47 ± 6.7 µmol/L with
D-NAME and 72 ± 15 µmol/L with
L-NAME. No further change was observed when 10
µmol/L isoproterenol was used. Isoproterenol caused the same increase
in dialysate lactate concentration during L-NAME
and D-NAME treatments (Fig. 2, bottom).
In adipose tissue, the dialysate glycerol concentration before
isoproterenol stimulation tended to be greater with L-NAME
than with D-NAME (70 ± 8.9 µmol/L with
D-NAME; 93 ± 18 µmol/L with L-NAME;
P = 0.05). During 1 µmol/L isoproterenol, the
dialysate glycerol concentration was 47 ± 6.7 µmol/L with
D-NAME and 72 ± 15 µmol/L with
L-NAME. The response of the dialysate glycerol
concentration to isoproterenol was moderately augmented with
L-NAME (Fig. 2, middle). During 1
µmol/L isoproterenol, the dialysate glycerol concentration was
210 ± 18 µmol/L with D-NAME and 264
± 24 µmol/L with L-NAME.
L-NAME had no significant effect on the dialysate
lactate concentration (Fig. 2, bottom).
In skeletal muscle, the norepinephrine concentration without
isoproterenol was 0.84 ± 0.14 nmol/L with D-NAME and
0.82 ± 0.15 nmol/L with L-NAME. Isoproterenol caused
a dose-dependent increase in dialysate norepinephrine. The response
(Fig. 3) was augmented by
L-NAME (P = 0.02). In skeletal muscle,
dialysate norepinephrine during 1 µmol/L isoproterenol was 0.73
± 0.17 nmol/L with D-NAME and 1.3 ± 0.15
nmol/L with L-NAME.
|
In skeletal muscle, epinephrine caused a marked decrease in tissue
perfusion (Fig. 4, top). With
D-NAME, the ethanol ratio was 0.05 ± 0.014
without epinephrine and increased to 0.1 ± 0.012 with 1 µmol/L
epinephrine. This response was not modulated by
L-NAME. During 1 µmol/L epinephrine, the
dialysate glycerol concentration was 54 ± 9.7 µmol/L with
D-NAME and 73 ± 15 µmol/L with
L-NAME (P = 0.1; Fig. 4, middle). Epinephrine caused the same increase in the
dialysate lactate concentration during L-NAME and
D-NAME treatments (Fig. 4, bottom).
Without epinephrine, the dialysate glucose concentration was 1.7
± 0.15 mmol/L with D-NAME and 1.6 ± 0.1
mmol/L with L-NAME. With 1 µmol/L epinephrine,
dialysate glucose decreased to a similar degree with
D-NAME and L-NAME
(0.83 ± 0.13 mmol/L with D-NAME; 0.98
± 0.12 mmol/L with L-NAME).
|
, bottom). Without epinephrine,
the dialysate glucose concentrations were 1.3 ± 0.27 and 1.3
± 0.28 mmol/L with D- and
L-NAME, respectively. With 1 µmol/L
epinephrine, the dialysate glucose decreased to 0.90 ± 0.17 and
0.92 ± 0.27 mmol/L with D-and
L-NAME, respectively. Nitroprusside sensitivity and NOS inhibition
In skeletal muscle, nitroprusside caused a marked vasodilation,
indicated by a reduction in the ethanol ratio (Fig. 5). At the highest dose of nitroprusside,
the ethanol ratio was 0.02 ± 0.01 with D-NAME and
0.03 ± 0.003 with L-NAME. In the absence of
nitroprusside, the dialysate glycerol concentration was 45 ± 8.6
µmol/L with D-NAME and 70 ± 15 µmol/L with
L-NAME. Nitroprusside attenuated the difference in
dialysate glycerol concentration between L- and
D-NAME (38 ± 4.2 µmol/L with D-NAME and
45 ± 4.7 µmol/L with L-NAME). Without
nitroprusside, the dialysate lactate concentration was 1.7 ± 0.1
mmol/L with D-NAME and 2.0 ± 0.2 mmol/L with
L-NAME. Nitroprusside caused a marked decrease in the
dialysate lactate concentration to 1.0 ± 0.1 and 0.9 ± 0.1
mmol/L with D- and L-NAME, respectively. With
D-NAME, the dialysate glucose concentration was 1.3 ±
0.1 mmol/L in the absence of nitroprusside and 2.3 ± 0.15 mmol/L
in the presence of 4 mmol/L nitroprusside (P < 0.001).
A similar response of the dialysate glucose concentration to
nitroprusside was seen in the presence of
L-NAME.
|
). With D-NAME, the
dialysate glycerol concentration decreased from 109 ± 9.6
µmol/L at baseline to 65 ± 2.8 µmol/L during 4 mmol/L
nitroprusside (P < 0.01). An almost identical response
was observed in the presence of L-NAME (Fig. 5).
Dialysate lactate concentrations were similar during
D- and L-NAME applications
and did not change significantly with nitroprusside. In the presence of
D-NAME, the dialysate glucose concentration was
1.3 ± 0.2 mmol/L at baseline and 2.0 ± 0.2 mmol/L with 4
mmol/L nitroprusside (P < 0.01). The response was
similar with L-NAME. Discussion
Our main finding was that NOS inhibition with L-NAME abolished isoproterenol-induced vasodilation in skeletal muscle. The interaction between adrenergic stimulation and NOS inhibition on perfusion was less pronounced in adipose tissue. Furthermore, NOS inhibition augmented the ß- adrenergic receptor-mediated increase in dialysate glycerol. In contrast, the effect of adrenergic stimulation on dialysate lactate was not modulated by NOS inhibition. Finally, NOS inhibition enhanced the ß2-adrenoreceptor-mediated increase in the dialysate norepinephrine concentration. These interactions were observed at physiologically relevant concentrations of isoproterenol and epinephrine.
In this study we focused on the interaction between the autonomic
nervous system and NO in peripheral tissues. We found that NOS
inhibition achieved by applying L-NAME through a
microdialysis probe did not cause a major decrease in basal perfusion
of adipose tissue and skeletal muscle. However, L-NAME had
a tissue-specific effect on the response to adrenergic stimulation. In
skeletal muscle, NOS inhibition almost completely abolished
isoproterenol- induced vasodilation. This finding is consistent
with earlier studies showing a reduced vasodilator response to
intrabrachial isoproterenol infusion during NOS inhibition
(8). Similarly, NO inhibition applied through a
microdialysis probe attenuates exercise-induced vasodilation in
skeletal muscle (20), which is in part
ß2-adrenergic receptor mediated. In sc adipose
tissue, the interaction between isoproterenol and NOS inhibition on
perfusion was less pronounced. The interaction between NOS inhibition
and adrenergic receptor stimulation in muscle perfusion was not evident
when epinephrine was used. This observation suggests that the effect on
vascular -adrenergic receptors dominates when epinephrine is applied
to the interstitial space and that this response is less affected by
basal NO release. The responses to epinephrine applied through the
microdialysis probe were remarkable in that they differed qualitatively
from responses to intraarterial infusions. Intraarterial epinephrine is
known to cause forearm vasodilation (21).
In addition to the modulating effect of NOS inhibition on tissue perfusion, our data suggest that NO influences the metabolic response to adrenergic stimulation. Metabolite concentrations in the interstitial space are influenced by production and removal from the interstitial space. The latter is strongly influenced by blood flow (11). Both isoproterenol and epinephrine elicited a dose-dependent increase in the dialysate glycerol concentration. With isoproterenol, the dialysate glycerol concentration increased, although blood flow, and thus efflux of glycerol from the interstitial space (11), increased. Therefore, ß-adrenergic receptor stimulation increased glycerol production, suggesting an increase in lipolysis. The effects of isoproterenol and epinephrine on the dialysate glycerol concentration were augmented by L-NAME. The interaction between NOS inhibition and isoproterenol on dialysate glycerol is difficult to interpret, because NOS inhibition had a strong effect on the blood flow response to isoproterenol (11). However, L-NAME enhanced the effect of epinephrine on dialysate glycerol even in the absence of a significant effect on blood flow. Thus, NO seems to restrain ß-adrenergic receptor-mediated lipolysis in abdominal adipose tissue and skeletal muscle. Similarly, NOS inhibition was shown to increase basal glycerol release (22). Further evidence for preferential activation of the lipolytic pathway stems from our observation that NOS inhibition does not potentiate the effects of isoproterenol and epinephrine on the dialysate lactate concentration. The decrease in the dialysate glucose concentration with ß-adrenergic stimulation is consistent with increased cellular glucose uptake. The dialysate glucose concentration was not significantly influenced by NOS inhibition.
The interaction between adrenergic receptor stimulation and NOS inhibition in peripheral tissues could result from a direct effect on postsynaptic mechanisms and an indirect effect on norepinephrine release (23). Stimulation of postsynaptic ß2-adrenergic receptors located at vascular smooth muscle cells causes vasodilation through an increase in the intracellular cAMP concentration. It has been suggested that the relaxant effect of cAMP in smooth muscle cells may be potentiated by NO (24). In addition to the direct effect on vascular smooth muscle cells, stimulation of endothelial ß2-adrenergic receptors increases NO production (9, 25). This component can be abolished by NOS inhibition and may be in part responsible for the findings of our study.
Stimulation of presynaptic ß2-adrenergic receptors augments norepinephrine release from adrenergic neurons (23, 26). The indirect norepinephrine-releasing effect of ß2-adrenoreceptor stimulation tends to counteract the vasodilatory effect. In our study NOS inhibition augmented the effect of ß2-adrenergic receptor stimulation on the dialysate norepinephrine concentration. An increase in norepinephrine release or a decrease in overflow from the interstitial space into the systemic circulation may be contributory (27). Regardless of what mechanism raises the interstitial norepinephrine concentration, the concentration to which the adrenergic receptors are exposed is increased. Earlier studies in animals using different methodology showed a restraining effect of NO on norepinephrine release (7). In this study we assessed the effect of short-term NO inhibition on the sensitivity to adrenergic agonists and on norepinephrine turnover. It is possible that long-term NO inhibition or pathological states that are associated with impaired NO production have an effect on the response to adrenergic stimulation different from the effect of short-term NO inhibition.
We conclude that in the resting skeletal muscle, NOS inhibition strongly attenuates ß2-adrenoreceptor-mediated vasodilation. This interaction is less pronounced in abdominal adipose tissue. Moreover, NO inhibition enhances ß-adrenergic receptor-mediated lipolysis in skeletal muscle and adipose tissue. These effects of NO inhibition appear to be at least in part mediated through an increase in the interstitial norepinephrine concentration (28). The data are consistent with the idea that NO is important in modulating and ameliorating sympathetic effects in peripheral tissues. Negative effects of excessive sympathetic stimulation may be enhanced in the setting of impaired NO production.
Footnotes
1 This work was supported in part by a grant from the Deutsche
Forschungsgemeinschaft (Jo 284/3–1). 
Received August 17, 2000.
Revised October 12, 2000.
Revised February 15, 2001.
Accepted March 2, 2001.
References
This article has been cited by other articles:
 |
|
 |
|
  S. Engeli, M. Boschmann, F. Adams, G. Franke, K. Gorzelniak, J. Janke, F. C. Luft, and J. Jordan Dissociation between Adipose Nitric Oxide Synthase Expression and Tissue Metabolism J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2706 - 2711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Birkenfeld, M. Boschmann, C. Moro, F. Adams, K. Heusser, J. Tank, A. Diedrich, C. Schroeder, G. Franke, M. Berlan, et al. {beta}-Adrenergic and Atrial Natriuretic Peptide Interactions on Human Cardiovascular and Metabolic Regulation J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 5069 - 5075. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Engeli, M. Boschmann, P. Frings, L. Beck, J. Janke, J. Titze, F. C. Luft, M. Heer, and J. Jordan Influence of Salt Intake on Renin-Angiotensin and Natriuretic Peptide System Genes in Human Adipose Tissue Hypertension, December 1, 2006; 48(6): 1103 - 1108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. K. McConell, N. N. Huynh, R. S. Lee-Young, B. J. Canny, and G. D. Wadley L-Arginine infusion increases glucose clearance during prolonged exercise in humans Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E60 - E66. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Boschmann, S. Engeli, F. Adams, G. Franke, F. C. Luft, A. M. Sharma, and J. Jordan Influences of AT1 receptor blockade on tissue metabolism in obese men Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R219 - R223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Boschmann, S. Engeli, F. Adams, K. Gorzelniak, G. Franke, S. Klaua, U. Kreuzberg, S. Luedtke, R. Kettritz, A. M. Sharma, et al. Adipose Tissue Metabolism and CD11b Expression on Monocytes in Obese Hypertensives Hypertension, July 1, 2005; 46(1): 130 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Birkenfeld, M. Boschmann, C. Moro, F. Adams, K. Heusser, G. Franke, M. Berlan, F. C. Luft, M. Lafontan, and J. Jordan Lipid Mobilization with Physiological Atrial Natriuretic Peptide Concentrations in Humans J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3622 - 3628. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Engeli, J. Janke, K. Gorzelniak, J. Bohnke, N. Ghose, C. Lindschau, F. C. Luft, and A. M. Sharma Regulation of the nitric oxide system in human adipose tissue J. Lipid Res., September 1, 2004; 45(9): 1640 - 1648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Schroeder, F. Adams, M. Boschmann, J. Tank, S. Haertter, A. Diedrich, I. Biaggioni, F. C. Luft, and J. Jordan Phenotypical evidence for a gender difference in cardiac norepinephrine transporter function Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2004; 286(5): R851 - R856. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Tank, A. Diedrich, E. Szczech, F. C. Luft, and J. Jordan {alpha}-2 Adrenergic Transmission and Human Baroreflex Regulation Hypertension, May 1, 2004; 43(5): 1035 - 1041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-L. Ardilouze, B. A. Fielding, J. M. Currie, K. N. Frayn, and F. Karpe Nitric Oxide and {beta}-Adrenergic Stimulation Are Major Regulators of Preprandial and Postprandial Subcutaneous Adipose Tissue Blood Flow in Humans Circulation, January 6, 2004; 109(1): 47 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Boschmann, J. Steiniger, U. Hille, J. Tank, F. Adams, A. M. Sharma, S. Klaus, F. C. Luft, and J. Jordan Water-Induced Thermogenesis J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 6015 - 6019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Boschmann, J. Jordan, F. Adams, N.-J. Christensen, J. Tank, G. Franke, M. Stoffels, A. M. Sharma, F. C. Luft, and S. Klaus Tissue-Specific Response to Interstitial Angiotensin II in Humans Hypertension, January 1, 2003; 41(1): 37 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Boschmann, C. Schroeder, N. J. Christensen, J. Tank, G. Krupp, I. Biaggioni, S. Klaus, A. M. Sharma, F. C. Luft, and J. Jordan Norepinephrine Transporter Function and Autonomic Control of Metabolism J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 5130 - 5137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Hijmering, E. S. G. Stroes, J. Olijhoek, B. A. Hutten, P. J. Blankestijn, and T. J. Rabelink Sympathetic activation markedly reduces endothelium-dependent, flow-mediated vasodilation J. Am. Coll. Cardiol., February 20, 2002; 39(4): 683 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Tank, A. Diedrich, C. Schroeder, M. Stoffels, G. Franke, A. M. Sharma, F. C. Luft, and J. Jordan Limited Effect of Systemic {beta}-Blockade on Sympathetic Outflow Hypertension, December 1, 2001; 38(6): 1377 - 1381. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
