| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
INTEGRATIVE |
Departments of
1 Internal Medicine
2 Anaesthesiology, Mayo Clinic College of Medicine, Rochester, MN55905, USA
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
16 min). Prior to the infusion, there were no differences in 24-h Na+ excretion between Gly16 and Arg16 subjects (Gly16, 183 ± 21 mmol; Arg16, 184 ± 20 mmol); however, systolic blood pressure (SBP) was significantly higher in Gly16 than Arg16 subjects with no differences observed in diastolic blood pressure (DBP) or mean arterial pressure (MAP) (SBP: Gly16, 117 ± 3 mmHg; Arg16, 109 ± 2 mmHg; DBP: Gly16, 78 ± 2 mmHg; Arg16, 77 ± 2 mmHg; MAP: Gly16, 90 ± 2 mmHg; Arg16, 89 ± 2 mmHg). With rapid saline infusion, MAP increased in both genotype groups (Gly16, 6.7%; Arg16, 3.4%; P > 0.05). In the 3 h following Na+ infusion, Na+ excretion was less in Gly16 when compared to Arg16 subjects, with a trend towards significance when expressed as total Na+ excreted (Gly16, 66 ± 7 mmol; Arg16, 85 ± 9 mmol; P
= 0.07), and a significant difference when expressed as a fraction of the administered load (Gly16, 0.18 ± 0.02; Arg16, 0.28 ± 0.03; P < 0.01). These results suggest that the Arg16Gly polymorphism of the ß2AR is associated with differences in natriuretic response to rapid saline infusion, which may influence long-term regulation of blood pressure.
(Received 16 February 2006;
accepted after revision 17 May 2006;
first published online 25 May 2006)
Corresponding author E. M. Snyder: Division of Cardiovascular Diseases, Mayo Clinic and Foundation, 200 1st Street, SW Rochester, MN 55905, USA. Email: snyder.eric{at}mayo.edu
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Several polymorphisms of the ß2AR have been studied in humans. The most functional variant of the ß2AR appears to be an isoleucine substitution for threonine at position 164; however, this occurs in less than 3% of Caucasians (Green et al. 1995). An arginine (Arg) to glycine (Gly) substitution at amino acid 16 and a glutamine to glutamate substitution at amino acid 27 have also been described and studied in detail (Green et al. 1993, 1994, 1995). Human studies suggest that subjects homozygous for Arg at amino acid 16 (Arg16) may have reduced ß2AR function when compared to subjects homozygous for Gly at this position (Gly16) (Dishy et al. 2001; Garovic et al. 2003; Tang et al. 2003; Eisenach et al. 2005; Snyder et al. 2005a, 2006).
Specifically, Arg16 subjects show attenuated vasodilatation during infusion of a ß-agonist in the brachial artery and venous circulation when compared to Gly16 subjects (Dishy et al. 2001; Garovic et al. 2003). Although Arg16 subjects tend to have reduced vasodilatation when compared to Gly16 subjects, we have previously found that the Arg16 group had lower arterial blood pressure, which was not dependent on differences in cardiac output between the genotype groups (Bray et al. 2000; Snyder et al. 2005a). Therefore, our observed difference in blood pressure between the genotype groups might be attributed to differences in renal sodium handling (Snyder et al. 2005b).
In this context, we sought to determine whether there was an association between genetic variation of the ß2AR at amino acid 16 and the natriuretic response to rapid fluid loading. We hypothesized that subjects homozygous for glycine at amino acid 16 of the ß2AR would have greater sodium reabsorption and therefore less sodium excretion when compared to subjects homozygous for arginine at this position following rapid fluid loading.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The protocol was reviewed and approved by the Mayo Clinic Institutional Review Board, all participants provided informed consent prior to participation, and all aspects of the study conformed to the Declaration of Helsinki. Caucasian subjects who were matched for age, sex and level of physical activity were recruited from a pool of subjects previously genotyped for the Arg16Gly polymorphism of the ß2AR (Bray et al. 2000).
Protocol
The study involved two separate experimental sessions, one for screening and the second for rapid saline infusion. The screening tests included an incremental cycle ergometry test to exhaustion (to rule out cardiovascular abnormalities), a complete blood count (CBC, to rule out anaemia) and, in women, a pregnancy test. The maximal cycle ergometry test was performed while oxygen uptake 
and the elimination of carbon dioxide were measured continuously (Medical Graphics, St Paul, MN, USA). Two-minute increments were used for the cycle ergometry test until a perceived exertion rating of 18 (out of a possible 20) was achieved (Borg, 1982). Following the screening tests, the subjects were given a 24-h urine collection container for the assessment of urine Na+ and creatinine (Cr) levels prior to their saline infusion test. At the end of the screening session, the subjects were instructed by a dietician how to maintain their usual sodium intake until the completion of the study.
Saline infusion
The subjects were instructed to report to the laboratory in a fasting state and all saline infusions were performed between 07.00 and 09.00 h. An 18-gauge venous catheter was inserted into a prominent antecubital vein for the rapid saline infusion and for blood sampling. Baseline measurements of cardiac output (CO), heart rate (HR) and systolic (SBP) and diastolic blood pressure (DBP) were obtained prior to the infusion. The subjects were instructed to void their bladders immediately before the infusion, and warmed saline was then infused intravenously (30 ml kg–1 over 15 min). During the saline infusion, oxygen saturation (SaO2), blood pressure (BP), HR and physical symptoms were continuously monitored and recorded every 2 min. Catecholamine (adrenaline and noradrenaline) levels were measured before and immediately after saline infusion from samples collected via the venous catheter. Following the infusion, repeat measures of CO and HR were obtained. Urine was collected every hour for 3 h following the infusion for the assessment of Na+ and Cr levels.
Data collection
Assessment of cardiovascular function. CO was assessed with a previously validated 8- to 10-breath acetylene rebreath technique using a 5-l anaesthesia bag containing 0.7% C2H2 and 9% He (Johnson et al. 2000; Bell et al. 2003). Briefly, a pneumotachograph was connected to a non-rebreathing Y-valve (Hans Rudolph, KC, MO) with the inspiratory port connected to a pneumatic switching valve (Hans Rudolph) which allowed for rapid switching from room air to the test gas mixture. Gases were sampled using a mass spectrometer (Perkin-Elmer) which was integrated with custom-made analysis software for the assessment of CO.
Blood pressure was recorded using the auscultation technique with the same technician performing all measures. Mean arterial pressure (MAP) was calculated using the equation: MAP = DBP + 1/3(SBP – DBP). Systemic vascular resistance (SVR) was calculated from MAP using the equation: SVR = MAP/CO. Heart rate was assessed using 12-lead electrocardiography (Marquette Electronics, Milwaukee, WI, USA).
Urine and plasma sodium and creatinine levels.
Urinary Na+ and Cr levels were determined with a 24-h collection prior to the saline infusion and a 3-h collection immediately following the saline infusion. For each urine collection, the time of collection and the volume and amount of Na+ and Cr were recorded and assessed. In addition, plasma Na+ and Cr levels were determined prior to the saline infusion. Both urine and plasma Na+ and Cr levels were assessed using ion-selective electrodes on a Hitachi 911 analyser (Roche, Indianapolis, IN, USA). The fractional excretion of sodium (FENa) was determined using the following equation:
|
|
Catecholamines. Adrenaline (ADR) and noradrenaline (NA) levels were assessed according to methods developed in the Mayo Clinic General Clinical Research Center immunochemical core laboratory and the methods of Sealey (1991). For ADR, our intra-assay coefficients of variation were 12.2% and 3.6% at 13.8 and 242 pg ml–1. Inter-assay coefficients of variation were 8.5% and 6.3% at 179 and 390 pg ml–1.
Data analysis
All statistical comparisons were performed using the SPSS statistical software package (v. 12.0, Chicago, IL, USA). Group demographics were compared using an independent samples Student's t test with an 
level of 0.05 to determine significance. A repeated measures ANOVA was performed to determine within group responses to rapid saline infusion, also with an level of 0.05 to determine significance. An independent samples t test was used to compare group differences in HR, BP and the natriuretic response to saline infusion with an level of 0.05 to determine significance for each. Before each t test and ANOVA, a Levene's test was performed to determine the homogeneity of the data. All data are presented as means ±
S.E.M., unless otherwise stated.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Individuals who were homozygous for Arg16 (n = 14) and Gly16 (n = 17) agreed to participate in the study and had no exclusion criteria. All subjects were healthy non-smokers, and not on medications. There were no differences between the genotype groups in age, weight, body mass index, body surface area or cardiovascular fitness; however, the Gly16 group was taller than the Arg16 group (Table 1).
|
At baseline, the Gly16 group had a higher systolic blood pressure than the Arg16 group but there were no significant differences in DBP, MAP, HR or SaO2 (Table 2). In addition, the Gly16 group had a higher CO and a lower SVR compared to the Arg16 group at baseline (Fig. 1). Rapid saline infusion resulted in an increase in ADR and NA levels but there were no differences between the genotype groups in these responses (baseline ADR: Arg16, 20 ± 4 3 pg ml–1; Gly16, 16 ± 3 pg ml–1; post-saline ADR: Arg16, 56 ± 13 3 pg ml–1; Gly16, 33 ± 7 pg ml–1; baseline NA: Arg16, 150 ± 15 3 pg ml–1; Gly16, 192 ± 27 pg ml–1, post-saline NA: Arg16, 329 ± 64 3 pg ml–1; Gly16, 325 ± 49 pg ml–1). Both groups exhibited increases in HR, SBP and MAP with saline infusion (as a percentage increase relative to the baseline level), but there were no differences between the genotype groups in these responses (HR: Arg16, 24 ± 7%; Gly16, 18 ± 4%; SBP: Arg16, 10 ± 3%; Gly16, 8 ± 3%, MAP: Arg16, 4 ± 2%; Gly16, 6 ± 3%). Both groups showed an increase in CO and decrease in SVR with rapid saline infusion, and at the end of the infusion, CO remained higher and SVR lower in the Gly16 group compared to the Arg16 group.
|
|
There were no differences in 24-h Na+ excretion between the Gly16 and Arg16 groups in the collection that was completed just prior to the infusion (Gly16, 183 ± 21 mmol; Arg16, 184 ± 20 mmol). On average, 2083 ml saline was infused in the Arg16 subjects over 16 min, while 2430 ml saline was infused in the Gly16 subjects over 17 min. The amount of Na+ infused averaged 321 mmol for the Arg16 subjects and 374 mmol for the Gly16 group, because the Gly16 group was slightly heavier (Arg16, 75 ± 4 kg; Gly16, 82 ± 3 kg; P = 0.16). Within 3 h after the infusion, the Arg16 group excreted 29% more Na+ than the Gly16 group, but the difference did not reach statistical significance (Fig. 2). The amount of Na+ excreted relative to the amount of Na+ infused was greatest in the Arg16 group (Arg16, 0.28 ± 0.03; Gly16, 0.18 ± 0.02, P < 0.01, Fig. 3). There were no differences in FENa during the 24-h urine collection or following rapid saline infusion; however, there was a trend towards increased FENa in the Arg16 group (Fig. 4).
|
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Epithelial Na+ channels
The ENaCs are found throughout the body including the lungs and the kidneys (Ciampolillo et al. 1996; Wallace et al. 2001, 2004; Planes et al. 2002). In the lungs the ENaCs are located on type-II alveolar cells and act to move Na+ and water from the alveolar airspace into the interstitium (Planes et al. 2002). In the kidneys, the ENaCs have been localized to the distal nephron and are thought to play a role in Na+ and blood pressure regulation (Koepke & DiBona, 1986; Snyder, 2000; Wallace et al. 2001, 2004). The importance of the ENaCs in renal sodium regulation and long-term blood pressure control is seen in psuedohypoaldosteronism type-1 and Liddle's syndrome. Psuedohypoaldosteronism type-1 is a loss-of-function mutation of the renal ENaCs which results in salt-wasting, whereas Liddle's syndrome is a gain-of-function mutation of the renal ENaC which results in increased salt-sensitivity and hypertension in humans (Shimkets et al. 1994; Kerem et al. 1999; Pradervand et al. 1999; Snyder, 2000). Although the renal ENaCs are primarily regulated by aldosterone, recent evidence has suggested that the ß2ARs also play an important role in renal Na+ regulation (Wallace et al. 2001, 2004).
ß2-Adrenergic control of renal ENaCs
In the kidneys, the ß2ARs have been localized to the inner-medullary collecting duct (IMCD) and influence sodium reabsorption both locally in response to circulating ADR as well as through central nervous system-mediated mechanisms (Koepke & DiBona, 1986; DiBona & Kopp, 1997; Wallace et al. 2004). Stimulation of the ß2ARs results in an increase in cAMP which increases the number of ENaCs on cell surfaces, or the probability that an ENaC will be open (Chen et al. 2001; Xi-Juan et al. 2002). Wallace et al. (2004) have recently elucidated three important facts that relate to ß2AR control of sodium reabsorption: (1) the ß2ARs are located on IMCD cells; (2) stimulation of the ß2ARs on these cells leads to an increase in cAMP; and (3) stimulation of the ß2ARs on IMCD cells augments anion secretion which is nearly abolished with ß-blockade.
In the present study we attempted to minimize the catecholamine response by warming the saline to body temperature just prior to the infusion; however, there was an increase in ADR and NA levels with the rapid fluid loading. This increase in catecholamine levels is most probably a result of mental stress caused by the infusion (and the discomfort associated with the infusion, i.e. chest tightness and shortness of breath).
Genetic variation of the ß2AR and blood pressure regulation
Previous research has suggested an association between the Gly16 allele of the ß2AR and elevated blood pressure in humans (Gratze et al. 1999; Bray et al. 2000; Snyder et al. 2005a). However, other studies have suggested a lack of relationship between genetic variation of the ß2AR and hypertension (Herrmann et al. 2002) or have associated the Arg16 allele with elevated blood pressure (Gratze et al. 1999). The findings of the present study confirm previous work from our laboratory showing that the Gly16 group has elevated blood pressure when compared to the Arg16 group (Snyder et al. 2006). Because of the contribution of Na+ reabsorption, CO and SVR to blood pressure regulation, the observed difference in blood pressure could be the result of differences in CO, although we have previously found that this does not fully explain the genotype related-differences (Snyder et al. 2005a). Genotype-related differences in SVR would also not explain why the Gly16 group has previously been shown to have elevated blood pressure. Previous work by us (Snyder et al. 2006) and others (Tang et al. 2003) suggests that the Gly16 group has enhanced receptor function, which would lower SVR as a result of peripheral vasodilatation, and lead to lower blood pressure.
Interestingly, we observed genotype-related differences in the natriuretic response to rapid saline infusion. Urinary Na+ excretion and FENa were borderline significant (P = 0.07 and 0.10, respectively); however, the amount of Na+ excreted relative to the amount of Na+ infused did reach statistical significance (P < 0.01). These findings of differences in the natriuretic response to saline infusion suggest that the genotype-related difference in blood pressure may be related to not only augmented CO but also increased Na+ reabsorption in the Gly16 group.
Limitations
A possible limitation to this study is the use of variation at one site of the ß2AR for comparison, rather than several sites. Although the use of single nucleotide polymorphisms (SNPs) is falling out of favour, we and others have been able to repeatedly reject the null hypothesis when examining phenotypic variation according to position 16. Of interest, recently Lanfear et al. (2005) found that Arg16 subjects had higher mortality rates when compared to Gly16 subjects following acute coronary syndrome when discharged with ß-blockade; however a specific reason for this difference was unclear. This larger clinical study underscores the importance of smaller mechanistic studies using SNPs to explain phenotypic differences which become particularly important in the clinical setting.
Implications
In a companion paper in this issue by Eisenach et al. (2006) salt restriction modified the genotype effect on vascular function, in agreement with previous observations (Garovic et al. 2003; Eisenach et al. 2004). Specifically, Eisenach et al. found that salt restriction increased SVR in Gly16 subjects and found that this intervention eliminated the previously observed augmentation in forearm blood flow in the Gly16 subjects relative to the Arg16 subjects (Garovic et al. 2003). This is an important finding and is probably related to the results of the present study. One could hypothesize that, under conditions of normal Na+ intake, Gly16 subjects have enhanced vascular relaxation which acts as a protective mechanism due to the higher Na+ reabsorption compared to Arg16 subjects. In contrast, with Na+ restriction, the Gly16 subjects have a reduction in vascular relaxation because of an attenuation in Na+ reabsorption. This hypothesis is supported by the work of Naslund et al. (1990), who found that Na+ restriction decreased forearm blood flow in response to addition of isoprenaline (isoproterenol), which was related to ß2AR function in vitro. The study by Eisenach and colleagues and the present study add to the growing body of evidence that common polymorphisms of the ß2AR influence BP regulation.
Conclusion
We found that subjects homozygous for glycine at amino acid 16 of the ß2AR had an attenuated natriuretic response to rapid saline infusion when compared to subjects homozygous for arginine at this position. In addition, we found that the Gly16 group had higher baseline SBP when compared to the Arg16 group. These findings suggest that the elevated blood pressure observed in the Gly16 group in this and previous studies may be a result of increased renal Na+ reabsorption due to enhanced ß2AR function and increased renal ENaC activity.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Bittner HB, Chen EP, Milano CA, Lefkowitz RJ & Van Trigt P (1997). Functional analysis of myocardial performance in murine hearts overexpressing the human beta 2-adrenergic receptor. J Mol Cell Cardiol 29, 961–967.[CrossRef][Medline]
Borg GAV (1982). A category scale with ratio properties for intermodal and interindividual comparisons. In Psychophysial Judgement and the Process of Perception ed. Geissler HG & Petzold P, pp. 25–34. Veb Deutsche Verlag Wissen Schaften, Berlin.
Bray
MS, Krushkal
J, Li
L, Ferrell
R, Kardia
S, Sing
CF, Turner
ST
&
Boerwinkle
E (2000). Positional genomic analysis identifies the beta2-adrenergic receptor gene as a susceptibility locus for human hypertension. Circulation
101, 2877–2882.
Bristow MR, Hershberger RE, Port JD, Minobe W & Rasmussen R (1989). Beta 1- and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium. Mol Pharmacol 35, 295–303.[Abstract]
Brodde OE (1991). Beta 1- and beta 2-adrenoceptors in the human heart: properties, function, and alterations in chronic heart failure. Pharmacol Rev 43, 203–242.[Medline]
Chen X, Eaton DC & Jain L (2001). Alveolar epithelial ion and fluid transport B-adrenergic regulation of amiloride-sensitive lung sodium channels. Am J Physiol Lung Cell Mol Physiol 282, L609–L620.
Chruscinski
AJ, Rohrer
DK, Schauble
E, Desai
KH, Bernstein
D
&
Kobilka
BK (1999). Targeted disruption of the beta2 adrenergic receptor gene. J Biol Chem
274, 16694–16700.
Ciampolillo F, McCoy DE, Green RB, Karlson KH, Dagenais A, Molday RS & Stanton BA (1996). Cell-specific expression of amiloride-sensitive, Na+-conducting ion channels in the kidney. Am J Physiol 271, C1303–C1315.[Medline]
DiBona
GF
&
Kopp
UC (1997). Neural control of renal function. Physiol Rev
77, 75–197.
Dishy
V, Sofowora
GG, Xie
HG, Kim
RB, Byrne
DW, Stein
CM
&
Wood
AJ (2001). The effect of common polymorphisms of the beta2-adrenergic receptor on agonist-mediated vascular desensitization. N Engl J Med
345, 1030–1035.
Eisenach
JH, Barnes
SA, Pike
TL, Sokolnicki
LA, Masuki
S, Dietz
NM, Rehfeldt
KH, Turner
ST
&
Joyner
MJ (2005). The Arg16/Gly beta2-adrenergic receptor polymorphism alters the cardiac output response to isometric exercise. J Appl Physiol
99, 1776–1781.
Eisenach
JH, Darrell
RS, Pike
TL, Johnson
CP, Snyder
ER
et al. (2006). Dietary sodium restriction and ß2-adrenergic receptor polymorphism modulate cardiovascular function in humans. J Physiol
574, 955–965.
Eisenach
JH, McGuire
AM, Schwingler
RM, Turner
ST
&
Joyner
MJ (2004). The Arg16/Gly beta2-adrenergic receptor polymorphism is associated with altered cardiovascular responses to isometric exercise. Physiol Genomics
16, 323–328.
Gaballa MA, Peppel K, Lefkowitz RJ, Aguirre M, Dolber PC, Pennock GD, Koch WJ & Goldman S (1998). Enhanced vasorelaxation by overexpression of beta 2-adrenergic receptors in large arteries. J Mol Cell Cardiol 30, 1037–1045.[CrossRef][Medline]
Gavoric
VD, Joyner
MJ, Dietz
NM, Boerwinkle
E
&
Turner
ST (2003). Beta2-adrenergic receptor polymorphism and nitric oxide-dependent forearm blood flow responses to isoproterenol in humans. J Physiol
546, 583–589.
Grandy
SA, Denovan-Wright
EM, Ferrier
GR
&
Howlett
SE (2004). Overexpression of human beta2-adrenergic receptors increases gain of excitation-contraction coupling in mouse ventricular myocytes. Am J Physiol Heart Circ Physiol
287, H1029–H1038.
Gratze
G, Fortin
J, Labugger
R, Binder
A, Kotanko
P, Timmermann
B, Luft
FC, Hoehe
MR
&
Skrabal
F (1999). Beta-2 adrenergic receptor variants affect resting blood pressure and agonist-induced vasodilation in young adult Caucasians. Hypertension
33, 1425–1430.
Green
SA, Cole
G, Jacinto
M, Innis
M
&
Liggett
SB (1993). A polymorphism of the human beta 2-adrenergic receptor within the fourth transmembrane domain alters ligand binding and functional properties of the receptor. J Biol Chem
268, 23116–23121.
Green SA, Turki J, Hall IP & Liggett SB (1995). Implications of genetic variability of human beta 2-adrenergic receptor structure. Pulm Pharmacol 8, 1–10.[Medline]
Green SA, Turki J, Innis M & Liggett SB (1994). Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry 33, 9414–9419.[CrossRef][Medline]
Herrmann SM, Nicaud V, Tiret L, Evans A, Kee F, Ruidavets JB, Arveiler D, Luc G, Morrison C, Hoehe MR, Paul M & Cambien F (2002). Polymorphisms of the beta2-adrenoceptor (ADRB2) gene and essential hypertension: the ECTIM and PEGASE studies. J Hypertens 20, 229–235.[CrossRef][Medline]
Iaccarino
G, Cipolletta
E, Fiorillo
A, Annecchiarico
M, Ciccarelli
M, Cimini
V, Koch
WJ
&
Trimarco
B (2002). Beta2-adrenergic receptor gene delivery to the endothelium corrects impaired adrenergic vasorelaxation in hypertension. Circulation
106, 349–355.
Johnson
BD, Beck
KC, Proctor
DN, Miller
J, Dietz
NM
&
Joyner
MJ (2000). Cardiac output during exercise by the open circuit acetylene washin method: comparison with direct Fick. J Appl Physiol
88, 1650–1658.
Kerem
E, Bistritzer
T, Hanukoglu
A, Hofmann
T, Zhou
Z, Bennett
W, MacLaughlin
E, Barker
P, Nash
M, Quittell
L, Boucher
R
&
Knowles
MR (1999). Pulmonary epithelial sodium-channel dysfunction and excess airway liquid in pseudohypoaldosteronism. N Engl J Med
341, 156–162.
Koepke
JP
&
Dibona
GF (1986). Central adrenergic receptor control of renal function in conscious hypertensive rats. Hypertension
8, 133–141.
Lanfear
DE, Jones
PG, Marsh
S, Cresci
S, McLeod
HL
&
Spertus
JA (2005). Beta2-adrenergic receptor genotype and survival among patients receiving beta-blocker therapy after an acute coronary syndrome. JAMA
294, 1526–1533.
Naslund T, Silberstein DJ, Merrell WJ, Nadeau JH & Wood AJ (1990). Low sodium intake corrects abnormality in beta-receptor-mediated arterial vasodilation in patients with hypertension: correlation with beta-receptor function in vitro. Clin Pharmacol Ther 48, 87–95.[Medline]
O'Donnell
SR
&
Wanstall
JC (1984). Beta-1 and beta-2 adrenoceptor-mediated responses in preparations of pulmonary artery and aorta from young and aged rats. J Pharmacol Exp Ther
228, 733–738.
Planes
C, Blot-Chabaud
M, Matthay
MA, Couette
S, Uchida
T
&
Clerici
C (2002). Hypoxia and beta 2-agonists regulate cell surface expression of the epithelial sodium channel in native alveolar epithelial cells. J Biol Chem
277, 47318–47324.
Pradervand
S, Barker
PM, Wang
Q, Ernst
SA, Beermann
F, Grubb
BR, Burnier
M, Schmidt
A, Bindels
RJ, Gatzy
JT, Rossier
BC
&
Hummler
E (1999). Salt restriction induces pseudohypoaldosteronism type 1 in mice expressing low levels of the beta-subunit of the amiloride-sensitive epithelial sodium channel. Proc Natl Acad Sci U S A
96, 1732–1737.
Sealey
JE (1991). Plasma renin activity and plasma prorenin assays. Clin Chem
37, 1811–1819.
Shimkets RA, Warnock DG, Bositis CM, Nelson-Williams C, Hansson JH, Schambelan M et al. (1994). Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell 79, 407–414.[CrossRef][Medline]
Snyder EM, Beck KC, Dietz NM, Eisenach JH, Joyner MJ, Turner ST & Johnson BD (2005a). Arg16Gly polymorphism of the beta-2 adrenergic receptor is associated with differences in cardiovascular function at rest and during exercise in humans. J Physiol 571, 121–130.[CrossRef][Medline]
Snyder EM, Joyner MJ, Turner ST & Johnson BD (2005b). Blood pressure variation in healthy humans: a possible interaction with beta-2 adrenergic receptor genotype and renal epithelial sodium channels. Med Hypotheses 65, 296–299.[CrossRef][Medline]
Snyder EM, Hulsebus ML, Turner ST, Joyner MJ & Johnson BD (2006). Genotype related differences in beta-2 adrenergic receptor density influence cardiac function. Med Sci Sports Exerc 38(5), 882–886.
Snyder PM (2000). Liddle's syndrome mutations disrupt cAMP-mediated translocation of the epithelial Na+ channel to the cell surface. J Clin Invest 105, 45–53.[Medline]
Tang W, Devereux RB, Kitzman DW, Province MA, Leppert M, Oberman A, Hopkins PN & Arnett DK (2003). The Arg16Gly polymorphism of the beta2-adrenergic receptor and left ventricular systolic function. Am J Hypertens 16, 945–951.[CrossRef][Medline]
Wallace
DP, Reif
G, Hedge
AM, Thrasher
JB
&
Pietrow
P (2004). Adrenergic regulation of salt and fluid secretion in human medullary collecting duct cells. Am J Physiol Renal Physiol
287, F639–F648.
Wallace
DP, Rome
LA, Sullivan
LP
&
Grantham
JJ (2001). cAMP-dependent fluid secretion in rat inner medullary collecting ducts. Am J Physiol Renal Physiol
280, F1019–F1029.
|
Acknowledgements |
|---|
This article has been cited by other articles:
|
|
 |
|
  E. M. Snyder, K. C. Beck, S. T. Turner, E. A. Hoffman, M. J. Joyner, and B. D. Johnson Genetic variation of the beta2-adrenergic receptor is associated with differences in lung fluid accumulation in humans J Appl Physiol, June 1, 2007; 102(6): 2172 - 2178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Eisenach, D. R. Schroeder, T. L. Pike, C. P. Johnson, W. G. Schrage, E. M. Snyder, B. D. Johnson, V. D. Garovic, S. T. Turner, and M. J. Joyner Dietary sodium restriction and {beta}2-adrenergic receptor polymorphism modulate cardiovascular function in humans J. Physiol., August 1, 2006; 574(3): 955 - 965. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
––
—
P < 0.05 versus baseline.
).
