| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536-0082
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Previous studies demonstrated that angiotensin II (ANG II) decreases body weight. This study examined whether ANG II regulates body weight through energy expenditure. Acute ANG II administration decreased oxygen consumption. To determine whether this effect was maintained, rats were infused with ANG II or saline for 14 days. Oxygen consumption was transiently decreased on day 1 of ANG II infusion; however, body weight and food intake were reduced for 14 days. In pair-feeding studies, reductions in food intake accounted for 63% of the effect of ANG II on body weight but did not influence systolic pressure, water intake, or oxygen consumption. With 28 days of ANG II infusion, differences in body weight between ANG II and control rats were of greater magnitude. An initial decrease in oxygen consumption was followed by a rebound increase. Coadministration of losartan prevented the effect of ANG II on body weight, food intake, blood pressure, and water intake. However, losartan only partially prevented ANG II reductions in oxygen consumption. These results demonstrate that ANG II transiently decreases oxygen consumption through mechanisms unrelated to food intake. With chronic ANG II exposure, energy expenditure may contribute to sustained reductions in body weight.
body weight; energy expenditure
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
ALL THE COMPONENTS of the renin-angiotensin system have been identified in adipose tissue (for review see Ref. 13), including angiotensinogen (5, 7, 8, 24), renin (18, 25), angiotensin-converting enzyme (11, 18, 25), and angiotensin II (ANG II) receptors (4, 10). Angiotensinogen mRNA expression in adipose tissue is regulated by a variety of factors, including insulin (20), fatty acids (23), glucocorticoids (1), and nutritional status (16). Processing enzymes important in ANG II formation have been localized to adipose tissue (24, 25), and ANG II peptides have been detected in adipocyte cell lines (24) and adipose tissue slices (3, 25). ANG II has been demonstrated to stimulate the release of prostacyclin from mature fat cells (12). Moreover, ANG II regulates enzymes important in fatty acid synthesis and metabolism (19). Collectively, these results have suggested the existence of a local renin-angiotensin system in adipose tissue (13), with the potential for adipocytes to produce and respond to ANG II. However, the functional significance of an adipose renin-angiotensin system and the potential physiological effects of ANG II at adipose tissue remain largely undefined.
As an approach to determine the physiological effects of ANG II at adipose tissue, previous studies in our laboratory examined the effect of chronic infusion of ANG II on the regulation of body weight in rats (6). Results from these studies demonstrated that chronic ANG II infusion resulted in a dose-dependent reduction in body weight that was independent of blood pressure (6). The ability of ANG II to decrease body weight was associated with reductions in food intake (2, 6); however, pair-feeding studies suggested that other mechanisms contribute to the effect of ANG II to regulate body weight (2). ANG II decreased body weight at doses that did not significantly elevate plasma ANG II concentration (6); thus it is conceivable that local adipose ANG II production could mediate this effect. The functional significance of this effect of ANG II was suggested to relate to disease states with heightened activity of the renin-angiotensin system, such as human heart failure or cirrhosis, where excessive peripheral metabolism and body wasting are significant clinical concerns.
Recent studies in our laboratory suggested that heightened sympathetic drive may contribute to the ability of ANG II to decrease body weight (14). After chronic ANG II infusion, plasma norepinephrine (NE) concentration was increased (14), catecholamine turnover was elevated in adipose tissue (unpublished observations), and NE release from slices of brown adipose tissue was increased (14). Collectively, these results suggested that ANG II may increase sympathetic drive to metabolically relevant tissues, including adipose tissue or skeletal muscle, and thereby increase peripheral energy expenditure. A well-known measure of peripheral energy expenditure is the determination of whole animal oxygen consumption using indirect calorimetry. The purpose of this study was to determine the effect of acute vs. chronic ANG II administration on whole body oxygen consumption as a measure of peripheral energy expenditure. We hypothesized that ANG II-mediated reductions in body weight resulted from stimulation of sympathetic drive to metabolically relevant tissues, ultimately contributing to elevations in peripheral energy expenditure. These results would support a metabolic effect of ANG II, potentially related to elevated peripheral energy expenditure in disease states with heightened activity of the renin-angiotensin system. Moreover, definition of the metabolic effect of ANG II would increase our understanding of the relevance of adipose ANG II formation.
| |
METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Animals. Male Sprague-Dawley rats (350-400 g; Harlan Sprague Dawley, Indianapolis, IN) were housed two per cage in an approved animal facility for 1 wk before use under a 12:12-h light-dark cycle and were given free access to food and water. During each experimental protocol, the rats were housed individually in cages for the daily (10 AM) measurement of body weight and food and water intake. For pair-feeding studies, a third group of rats was infused with saline and pair fed with ANG II-infused rats. All studies were approved by the Institutional Animal Care and Use Committee at the University of Kentucky.
Drug treatment.
For acute drug treatment, rats were injected with ANG II (20 or 200 µg/kg ip), isoproterenol (2.5 or 25 µg/kg ip), or an equivalent volume of vehicle (sterile saline). For chronic ANG II infusion, rats
were anesthetized with diethyl ether and shaved in the interscapular region, and osmotic minipumps [model 2001 (for 7-day infusion), model
2002 (for 14-day infusion), and model 2004 (for 28-day infusion), Alza] were implanted subcutaneously. Minipumps contained sterile saline (sham surgery), ANG II (260-400
ng · kg
1 · min1; Sigma, St.
Louis, MO), losartan (30 mg · kg1 · day1), or ANG
II + losartan and were primed according to the manufacturer's instructions before implantation to ensure immediate subcutaneous drug
delivery. The skin overlaying the minipump was closed with surgical
staples, and rats were allowed to recover on warmed heating pads.
Measurement of oxygen consumption.
Indirect calorimetry was used to measure energy expenditure. Conscious
rats were placed in a metabolic chamber (5 liters) for 45-120 min
for measurement of cumulative oxygen consumption. In initial studies
determining the acute effect of drugs, a single mass flowmeter was
used, and rats were placed in the chamber for 120 min. Thereafter, a
second mass flowmeter was placed in-line, and measurements were taken
for 45 min. After the chamber was opened for removal of the rat, the
system was allowed to reequilibrate for 15 min. Room air was circulated
(900 ml/min) through the chamber using a mass flowmeter and an air
pump. A second air pump was used to siphon a portion (300 ml/min) of
air from the chamber over desiccant and to an oxygen sensor and
analyzer (Applied Electrochemistry Technologies, Pittsburgh, PA). The
system was calibrated daily using the humidity of room air. DataQ
software was used to record measurements and to convert volts recorded
by the analyzer to percent oxygen. The cumulative oxygen consumption
over time in the chamber was recorded for each rat, then a peak oxygen
consumption value was taken from the plateau of individual plots of
cumulative oxygen consumption over time. Oxygen consumption for each
rat was calculated using the following formula: O2
consumption
(ml · kg1 · min1) = 600 × 
(l/min) × (%O2 amb 
%O2 eff)/M (kg) × (1 %O2 eff × 102), where is
flow, %O2 amb and %O2 eff represent percentage of ambient and effluent oxygen, respectively, and
M is body mass.
Measurement of systolic blood pressure. Systolic pressure was measured in ether-anesthetized rats with an inflatable tail cuff, a pressure and pulse transducer, and a recording polygraph. Three separate measurements of systolic pressure from each rat were averaged. Baseline systolic pressure was recorded before drug treatment or minipump implantation (baseline or predrug value), and systolic pressure was measured at the end of each study.
Statistical analysis. Values are means ± SE. For the acute drug studies, oxygen consumption data were analyzed using a one-way ANOVA with repeated measures on time. For the chronic drug studies, body weight, food and water intake, and oxygen consumption were analyzed using a two-way ANOVA with ANG II, losartan, or pair feeding as between-group factors and time as a within-group repeated measure. Post hoc analysis was performed using Tukey's multiple comparison test with significance at P < 0.05.
| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Acute administration of ANG II decreases oxygen consumption.
To validate the oxygen consumption apparatus, rats (n = 5/dose) were treated with the 
-receptor agonist isoproterenol at 2.5 or 25 µg/kg ip. The time course for oxygen consumption in rats for
120 min before and after injection of isoproterenol are illustrated in
Fig. 1. At 2.5 µg/kg, isoproterenol did
not significantly influence oxygen consumption compared with
pretreatment values (Fig. 1). At 25 µg/kg, isoproterenol resulted in
a significant increase in oxygen consumption from 80 to 120 min after
injection, demonstrating the sensitivity of the apparatus.
|
Effect of chronic administration of ANG II on oxygen consumption.
The previous experiment demonstrated that acute administration of ANG
II decreased oxygen consumption. To determine whether this acute effect
was maintained with chronic ANG II exposure and coincided with ANG II
regulation of blood pressure or body weight, we infused ANG II at 400 ng · kg1 · min1 or saline
for 14 days (n = 5 rats/group). Blood pressure was increased by chronic infusion of ANG II on day 7 and was
maintained at a greater level than controls on day 14 (Fig.
2). Within 4 days of ANG II infusion,
body weight was significantly decreased compared with control (Fig. 2).
Moreover, body weight was further reduced during week 2 of
ANG II infusion. Food intake decreased significantly within 3 days of
ANG II infusion and remained significantly decreased compared with
control over the time course of the study (Fig. 2). In rats receiving
saline, peak oxygen consumption was similar over 14 days of infusion
(Fig. 3). In contrast, a significant decrease in peak oxygen consumption induced by ANG II on day
1 was not maintained over the time course of the study. The data in Fig. 2B illustrate the oxygen consumption over the time
that rats were placed in the metabolic chamber for ANG II- and
saline-infused rats on day 2 of the study. Peak oxygen
consumption was calculated from the plateau portion of the curves and
was significantly decreased in ANG II-infused rats compared with
control. The slope of the curve for ANG II-infused rats was shifted to
the left.
|
|
|
|
1 · min1. Systolic
blood pressure was significantly increased in ANG II-infused rats
compared with saline controls (137 ± 6 and 171 ± 14 mmHg for saline- and ANG II-infused rats, respectively, P < 0.05). Body weight decreased compared with starting body weight and
compared with saline controls; on day 28, a 100-g (22%)
reduction in body weight was demonstrated in ANG II-infused rats
compared with saline controls (Fig.
6A). Food intake decreased by
36% within 2 days and remained reduced compared with saline controls
over the 28-day study (Fig. 6B). Water intake was increased
throughout the duration of ANG II exposure compared with saline
controls (Fig. 6C). Peak oxygen consumption decreased
initially in ANG II-infused rats from day 2 to day
10 compared with starting values and saline controls, increased
transiently from day 16 to day 18 of ANG II exposure, and thereafter was not different from saline controls (Fig.
7).
|
|
1 · day1), ANG II
(400 ng · kg1 · min1), or
ANG II + losartan (n = 5 rats/group) was
administered to four groups of rats for 7 days. Systolic blood pressure
was significantly increased in ANG II-infused rats compared with
controls (86 ± 6 and 137 ± 12 mmHg in saline- and ANG
II-infused rats, respectively, P < 0.05).
Administration of losartan alone had no significant effect on blood
pressure (data not shown); however, losartan administration prevented
ANG II-induced increases in systolic pressure (100 ± 10 mmHg in
rats treated with ANG II + losartan). ANG II + losartan totally prevented ANG II-induced reductions in body weight (Fig. 8A), food intake (Fig.
8B), and water intake (Fig. 8C). These results
demonstrate that the AT1 receptor mediates these effects of
ANG II. Chronic infusion of ANG II reduced peak oxygen consumption at
days 2 and 7 compared with saline control and
baseline (day 0) values (Fig.
9). ANG II + losartan prevented ANG
II-induced reductions in oxygen consumption on day 2.
However, losartan administration only partially prevented ANG
II-induced reductions in oxygen consumption on day 7.
|
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
The purpose of this study was to determine whether ANG II regulation of body weight was associated with regulation of oxygen consumption as a measure of peripheral energy expenditure. Results from this study demonstrate that acute and chronic exposure to ANG II transiently decreased oxygen consumption. However, initial reductions in oxygen consumption from chronic ANG II exposure were not maintained, and oxygen consumption returned to normal, despite a sustained elevation in blood pressure and reduction in food intake. Moreover, results from pair-feeding studies demonstrated that the observed decrease in oxygen consumption after ANG II exposure did not result from reductions in food intake. However, reductions in food intake did contribute significantly to ANG II-induced reductions in body weight. Finally, although ANG II regulation of food intake and body weight occurred through actions at the AT1 receptor, antagonism at the AT1 receptor only partially reversed the effect of ANG II on oxygen consumption. These results suggest that 1) ANG II regulates body weight initially through AT1-mediated reductions in food intake, 2) mechanisms unrelated to food intake may contribute to initial reductions in peripheral energy expenditure after ANG II exposure, and 3) with more chronic ANG II exposure, effects of ANG II on energy expenditure may contribute to further reductions in body weight.
The physiological effects of chronic ANG II exposure on the cardiovascular system are well known and include direct pressor effects at vascular smooth muscle, an increase in the synthesis and secretion of aldosterone, stimulation of sympathetic neurotransmission, and the induction of cardiac and vascular hypertrophy. Several of these and other effects of ANG II may have an impact on peripheral energy expenditure. First, the direct vasoconstrictor effect of ANG II at AT1 receptors on vascular smooth muscle cells would predictably reduce blood flow in the periphery and, thereby, change the rate of supply of nutrients to muscle and removal of metabolic products (9, 22). After acute ANG II infusion, previous investigators demonstrated that microvascular blood flow was reduced in the perfused rat hindlimb (9, 22). However, evidence suggested that vasoconstriction produced by low-dose ANG II actually increased basal oxygen uptake in skeletal muscle (9, 22). On the basis of previous findings in the literature, we suggest that vasoconstriction in response to ANG II did not contribute to the observed transient decrease in oxygen consumption in this study. Moreover, despite sustained increases in blood pressure with ANG II exposure, oxygen consumption returned to pretreatment values, suggesting that ANG II regulation of oxygen consumption is not totally dependent on pressure effects of the peptide. Finally, given that the infused doses of ANG II were sufficient for direct pressor effects and would therefore elicit baroreceptor-mediated reductions in sympathetic outflow, even a normal level of oxygen consumption in ANG II-infused rats may have been inappropriately high.
A second mechanism potentially contributing to the ability of ANG II to regulate oxygen consumption includes regulation of hypothalamic thermoregulatory regions in the brain. A reduction in oxygen consumption, coupled with a decrease in colonic temperature and an increase in tail skin temperature, was previously reported after a similar dose of acutely administered ANG II (17, 26). The observed reduction in oxygen consumption after acute ANG II administration was suggested to result from a hypothalamic effect of the peptide to increase heat dissipation and reduce heat production (17, 26). Our results agree with these previous findings and demonstrate that acute administration of ANG II reduced oxygen consumption. Additionally, results from this study extend previous findings by demonstrating that these acute responses to ANG II are evident during week 1 of exposure to the peptide. However, reductions in oxygen consumption were not maintained with more chronic ANG II exposure. In contrast, transient increases in oxygen consumption were observed with more chronic ANG II infusion. These results suggest that the effects of the peptide in thermoregulatory regions of the hypothalamus on acute exposure may be overridden or lost with chronic ANG II exposure. However, chronic ANG II exposure continued to increase water intake, an additional effect of ANG II mediated through the hypothalamus.
A third mechanism potentially contributing to the ability of ANG II to regulate oxygen consumption includes the observed effects of chronic ANG II infusion to decrease food intake. Previous investigators have demonstrated that pair feeding of rats to food intake levels of ANG II-infused rats accounted for ~70% of the body weight-reducing effects of the peptide (2); however, oxygen consumption was not measured in previous studies. The authors suggested that the remaining 30% reduction in body weight may arise from stimulation of sympathetic nervous system activity by ANG II and resultant increases in basal metabolism. In agreement with previous findings, our results demonstrate that reductions in food intake accounted for 63% of the decrease in body weight after 14 days of ANG II infusion. It is well documented that, under conditions of prolonged fasting or food restriction, metabolic rate may eventually decrease to compensate partially for the energy deficit (15). Thus ANG II-mediated reductions in food intake could conceivably contribute to any observed decrease in oxygen consumption. In agreement, in this study the initial reduction in oxygen consumption with chronic ANG II exposure occurred coincidentally with reductions in food intake. However, despite the sustained reduction in food intake with chronic ANG II exposure, oxygen consumption returned to normal values. More importantly, in rats pair fed to food intake levels of ANG II-infused rats, oxygen consumption did not change from baseline, demonstrating that ANG II-mediated reductions in food intake are not responsible for the observed decrease in oxygen consumption.
A fourth mechanism potentially contributing to the effects of ANG II to regulate oxygen consumption includes stimulation of the sympathetic nervous system. A well-documented effect of ANG II is an increase in central nervous system sympathetic outflow as well as stimulation of NE release from peripheral sympathetic nerve terminals (3, 14). Our previous results demonstrated that ANG II can increase NE release from sympathetic nerve terminals innervating rat brown adipose tissue (3) and that these effects of ANG II are increased on chronic ANG II exposure (14). Moreover, previous studies have demonstrated that chronic ANG II infusion increases catecholamine turnover as an index of sympathetic activity in a variety of tissues (21), including adipose tissue (unpublished observations). Stimulation of sympathetic outflow to adipose tissue would increase lipolysis and provide an efficient fuel for thermogenesis and, thereby, could potentially increase oxygen consumption. However, results from this study demonstrate that ANG II infusion initially decreased, rather than increased, peripheral energy expenditure. In contrast, with longer-term ANG II exposure, oxygen consumption transiently increased and then returned to normal values, despite sustained increases in blood pressure and reductions in food intake. Moreover, when ANG II was infused for 28 days, further reductions in body weight during week 2 of infusion coincided with the rebound increase in oxygen consumption. We suggest that the initial drop in oxygen consumption with ANG II infusion does not relate to the ability of the peptide to decrease body weight; however, with chronic ANG II exposure, increases in sympathetic outflow with resultant effects on energy expenditure may contribute to sustained ANG II-mediated reductions in body weight.
A fifth mechanism whereby ANG II may influence oxygen consumption relates to the effect of the peptide on adipocyte function. Previous investigators have demonstrated that ANG II, through direct or indirect mechanisms, can regulate factors produced by adipocytes, including prostacyclin (12) and leptin (6). The ability of ANG II to increase prostacyclin release from adipocytes has been implicated in the growth and differentiation of preadipocytes to adipocytes (11). As for leptin, previous studies in our laboratory have demonstrated a decrease in plasma leptin concentration after chronic ANG II infusion (6). In addition, previous investigators have demonstrated that ANG II can increase lipogenesis in 3T3-L1 adipocytes and human adipose cells (19), providing a greater amount of lipolytic fuel for energy expenditure. These effects of ANG II may collectively contribute to the ability of chronic ANG II exposure to regulate oxygen consumption.
In conclusion, results from this study demonstrate that acute and chronic exposure to ANG II decreases oxygen consumption. With chronic ANG II exposure, transient reductions in oxygen consumption coincided with reductions in food intake and body weight. However, pair-feeding studies demonstrated that transient decreases in oxygen consumption in response to ANG II were independent of reductions in food intake. In contrast, reductions in food intake did significantly contribute to ANG II-mediated decreases in body weight. With more chronic ANG II exposure (>2 wk), oxygen consumption returned to normal values and coincided with further reductions in body weight, suggesting that the long-term ability of the peptide to decrease body weight may relate to energy expenditure. The clinical implication of these results relates to disease states with heightened activity of the renin-angiotensin system, such as congestive heart failure, whereby elevations in systemic ANG II may contribute to the dysregulation of body weight. Moreover, the ability of elevated systemic ANG II to decrease oxygen consumption may relate to the diagnostically important and well-defined reduction in peak oxygen consumption in patients with congestive heart failure. Finally, these results suggest that local adipose ANG II production may bear physiological significance in the control of energy expenditure and resultant changes in body weight.
Perspectives
The renin-angiotensin system is a primary regulator of fluid and electrolyte balance, with aberrant activity of the system involved in the pathophysiology of hypertension and congestive heart failure. Given the cardiovascular importance of ANG II, considerable research has focused on local tissue production of the peptide. Previous studies in our laboratory have suggested the presence of local ANG II production in adipose tissue. However, the physiological significance of ANG II production by adipocytes remains undefined. In a search for an adipose-related function of ANG II, we used a well-known model of renovascular hypertension, namely, chronic infusion of ANG II to rats. Our results demonstrate that chronic infusion of ANG II to rats reduces body weight and that these effects of ANG II are magnified and maintained over time. In this study, we addressed whether ANG II-mediated reductions in body weight occur from an elevation in oxygen consumption as a measure of peripheral energy expenditure. Our rationale for examining energy expenditure in ANG II-treated rats was based on the observation that, in disease states associated with high circulating ANG II, such as end-stage congestive heart failure or cirrhosis, body wasting and/or cachexia are of significant clinical concern. Our results demonstrate that ANG II initially decreases oxygen consumption; however, oxygen consumption then increased above normal. Moreover, given the pressor effects and food-intake reducing properties of ANG II, even a normal level of oxygen consumption was probably inappropriately high. Although we did not define the precise mechanism of the effect of ANG II, our results demonstrate that these effects of ANG II were independent of food intake and mediated by the AT1 receptor. The broad implication of these findings is that chronic marked elevations in circulating ANG II may increase catabolism and contribute to cachexia. Future studies will determine the role of adipose-derived ANG II in the regulation of energy expenditure and body weight.| |
ACKNOWLEDGEMENTS |
|---|
This study was supported by National Heart, Lung, and Blood Institute Grant HL-58927.
| |
FOOTNOTES |
|---|
Address for reprint requests and other correspondence: L. A. Cassis, Rm. 434, Div. of Pharmaceutical Science, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082 (E-mail: lcassis{at}pop.uky.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.
10.1152/ajpregu.00261.2001
Received 8 February 2001; accepted in final form 10 October 2001.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Aubert, J,
Darimont C,
Safonova I,
Ailhaud G,
and
Negrel R.
Regulation by glucocorticoids of AGT gene expression and secretion in adipose cells.
Biochem J
328:
701-706,
1997.
2.
Brink, M,
Wellen J,
and
Delafontaine P.
Angiotensin II causes weight loss and decreases circulating insulin-like growth factor I in rats through a pressor-independent mechanism.
J Clin Invest
97:
2509-2516,
1996[ISI][Medline].
3.
Cassis, LA,
and
Dwoskin LP.
Presynaptic neuromodulation of neurotransmitter release by endogenous angiotensin II in brown adipose tissue.
J Neural Transm
34:
129-138,
1992.
4.
Cassis, LA,
Fettinger M,
and
Shenoy U.
Characterization and regulation of angiotensin II receptors in rat adipose tissue.
In: Recent Advances in Cellular and Molecular Aspects of Angiotensin Receptors, edited by Raizada M.. New York: Plenum, 1996, p. 39-47.
5.
Cassis, LA,
Lynch KR,
and
Peach MJ.
Localization and regulation of rat angiotensinogen messenger RNA.
Circ Res
62:
1259-1262,
1988
6.
Cassis, LA,
Marshall DE,
Fettinger MJ,
Rosenbluth B,
and
Lodder RA.
Mechanisms contributing to angiotensin II regulation of body weight.
Am J Physiol Endocrinol Metab
274:
E867-E876,
1998
7.
Cassis, LA,
Saye J,
and
Peach MJ.
Location and regulation of rat angiotensinogen messenger RNA.
Hypertension
11:
591-596,
1988
8.
Campbell, DJ,
and
Habener JF.
Cellular localization of AGT gene expression in brown adipose tissue and mesentery: quantification of messenger ribonucleic acid abundance using hybridization in situ.
Endocrinology
121:
1616-1626,
1987[Abstract].
9.
Clark, MG,
Colquhoun EQ,
Rattigan S,
Dora KA,
Eldershaw TPD,
Hall JL,
and
Ye J.
Vascular and endocrine control of muscle metabolism.
Am J Physiol Endocrinol Metab
268:
E797-E812,
1995
10.
Crandall, DL,
Herzlinger HE,
Saunders BD,
Zolotor RC,
Feliciano L,
and
Cervoni P.
Identification and characterization of ANG II receptors in rat adipocyte membranes.
Metabolism
42:
511-515,
1993[ISI][Medline].
11.
Crandall, DL,
Herzlinger HE,
Saunders BD,
and
Kral JG.
Developmental aspects of the adipose tissue renin-angiotensin system: therapeutic implications.
Drug Dev Res
32:
117-125,
1994.
12.
Darimont, C,
Vassaux G,
Aulhaud G,
and
Negrel R.
Differentiation of preadipose cells: paracrine role of prostacyclin upon stimulation of adipose cells by angiotensin II.
Endocrinology
135:
2030-2036,
1994[Abstract].
13.
Engeli, S,
Negrel R,
and
Sharma A.
Physiology and pathophysiology of the adipose tissue renin-angiotensin system.
Hypertension
35:
1270-1277,
2000
14.
English, V,
and
Cassis LA.
Facilitation of sympathetic neurotransmission contributes to angiotensin regulation of body weight.
J Neural Transm
106:
631-644,
1999.
15.
Even, PC,
and
Nicolaidis S.
Adaptive changes in energy expenditure during mild and severe feed restriction in the rat.
Br J Nutr
70:
421-431,
1993[ISI][Medline].
16.
Frederich, RCJ,
Kahn BB,
Peach MJ,
and
Flier JS.
Tissue-specific nutritional regulation of angiotensinogen in adipose tissue.
Hypertension
19:
339-344,
1992
17.
Fregly, MJ,
and
Rowland NE.
Effect of losartan potassium and deoxycorticosterone acetate on tail skin temperature response to acute administration of angiotensin II.
Pharmacol Biochem Behav
43:
229-233,
1992[ISI][Medline].
18.
Harp, JB,
and
DiGirolamo M.
Components of the renin-angiotensin system in adipose tissue: changes with maturation and adipose mass enlargement.
J Gerontol A Biol Sci Med Sci
50:
B270-B276,
1995[Abstract].
19.
Jones, BH,
Standridge MK,
and
Moustaid N.
Angiotensin II increases lipogenesis in 3T3-L1 and human adipose cells.
Endocrinology
138:
1512-1519,
1997
20.
Jones, BH,
Standridge MK,
Taylor JW,
and
Moustaid N.
Angiotensinogen gene expression in adipose tissue: analysis of obese models and hormonal and nutritional control.
Am J Physiol Regulatory Integrative Comp Physiol
273:
R236-R242,
1997
21.
Kline, RL,
Chow K,
and
Mercer PF.
Does enhanced sympathetic tone contribute to angiotensin II hypertension in rats?
Eur J Pharmacol
184:
109-118,
1990[ISI][Medline].
22.
Kuznetsova, LV,
Tomasek N,
Sigurdsson GH,
Banic A,
Erni D,
and
Wheatley AM.
Dissociation between volume blood flow and laser-Doppler signal from rat muscle during changes in vascular tone.
Am J Physiol Heart Circ Physiol
274:
H1248-H1254,
1998
23.
Safanova, I,
Aubert J,
Negrel R,
and
Ailhaud G.
Regulation by fatty acids of angiotensinogen gene expression in preadipose cells.
Biochem J
322:
235-239,
1997.
24.
Saye, JA,
Ragsdale NV,
Carey RM,
and
Peach MJ.
Localization of angiotensin peptide-forming enzymes of 3T3-F442A adipocytes.
Am J Physiol Cell Physiol
264:
C1570-C1576,
1993
25.
Shenoy, U,
and
Cassis LA.
Characterization of renin activity in brown adipose tissue.
Am J Physiol Cell Physiol
272:
C989-C999,
1997
26.
Wilson, KM,
and
Fregly MJ.
Angiotensin II-induced hypothermia in rats.
J Appl Physiol
58:
534-543,
1985
This article has been cited by other articles:
|
|
 |
|
  C. Yamin, O. Amir, M. Sagiv, E. Attias, Y. Meckel, N. Eynon, M. Sagiv, and R. E. Amir ACE ID genotype affects blood creatine kinase response to eccentric exercise J Appl Physiol, December 1, 2007; 103(6): 2057 - 2061. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Amir, R. Amir, C. Yamin, E. Attias, N. Eynon, M. Sagiv, M. Sagiv, and Y. Meckel Human, Environmental & Exercise: The ACE deletion allele is associated with Israeli elite endurance athletes Exp Physiol, September 1, 2007; 92(5): 881 - 886. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Porter and K. R. Potratz Effect of intracerebroventricular angiotensin II on body weight and food intake in adult rats Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2004; 287(2): R422 - R428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Williams, S. S. Dhamrait, P. T. E. Wootton, S. H. Day, E. Hawe, J. R. Payne, S. G. Myerson, M. World, R. Budgett, S. E. Humphries, et al. Bradykinin receptor gene variant and human physical performance J Appl Physiol, March 1, 2004; 96(3): 938 - 942. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
