| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Pharmacology and Toxicology, Wright State University School of Medicine, Dayton, OH 45450, USA
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
(Received 13 April 2005;
accepted after revision 2 June 2005; first published online 8 June 2005)
Corresponding author Yanfang Chen: Department of Pharmacology and Taxicology, 3640 Colonel Glenn Highway, Wright State University School of Medicine, Dayton, OH 45435-0001, USA. Email: yanfang.chen{at}wright.edu
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Questions as to the physiological function of the AT1a and AT11b receptors have relied on molecular genetic manipulations because the receptors cannot be differentiated with pharmacological agents. Over-expression of AT1a receptors in brain resulted in enhanced cardiovascular sensitivity to central Ang II stimulation (Lazartigues et al. 2002). In contrast, deletion of the AT1a receptor produced animals with low BP, increased water intake and abnormal kidney function (Ito et al. 1995; Oliverio et al. 2000b). Davisson et al. (2000) reported that CNS AT1b receptors are important in drinking behaviour as the drinking response to central administration of Ang II was absent in AT1b-deficient mice. There is also evidence that Ang AT1b receptors are important in BP control (Oliverio et al. 1997; Zhou et al. 2003). AT1b receptors are present in arterioles and neuroendocrine tissues as determined using PCR with enzyme restriction digest (Zhou et al. 2003, 2005). In fact, Ang AT1b appears to the dominant form in the vasculature (Zhou et al. 2003, 2005). Chronic blockade of AT1 with losartan reduced BP in AT1a–/– mice (Oliverio et al. 1997) and BP was lower in the combined AT1a/AT1b knockout mice as compared to animals with the single AT1a gene deletion (Oliverio et al. 1998). Data also showed that AT1a–/– mice are more sensitive to the effects of dehydration and salt loading (Oliverio et al. 2000a) in terms of BP and CNS activation (Morris et al. 2001). This along with other data suggests that both Ang AT1a and AT1b signalling participate in the osmotic control of blood pressure.
The objective of the present study was to further characterize the role of AT1b receptors in osmotic regulation of BP by conducting studies in Ang AT1a–/– mice. We examined the effect of a vascular osmotic challenge on BP, heart rate (HR) and plasma VP concentration, as well as the effect of acute VP injection on BP and HR.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Adult male AT1a–/– and AT1a+/+ mice (27–35 g) were used for these studies. Animals were generated from a breeding colony maintained at Wright State University. The original founders were provided by Dr Thomas Coffman (Duke University, Durham, NC, USA) (Ito et al. 1995). The genotype was determined by PCR analysis of genomic DNA isolated from tail tissue according to previously reported methods (Ito et al. 1995). Mice were housed singly at 22°C and 100 Lux, under a 12-h light–12-h dark cycle with access to water and standard mouse chow (0.4% NaCl, Harlan Teklad, Madison, WI, USA) ad libitum. The investigation conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication no. 85–23, revised 1996).
Measurement of blood pressure and heart rate
Mean arterial pressure (MAP) and HR were measured in mice using direct carotid arterial catheters. Detailed methods for catheter implantation have been previously described (Li et al. 1999; Joaquim et al. 2004). Briefly, mice were anaesthetized with a ketamine–xylazine mixture (70: 6 mg kg–1, I.M.) and surgery was conducted using a dissection microscope. A microrenathane catheter (o.d., 0.635 mm; Braintree Scientific, Inc., Braintree, MA, USA) was inserted into the carotid artery. The catheter was covered with a spring and attached to a swivel at the top of the cage. The catheter was connected through a flow-through BP transducer to a syringe pump. Heparinized saline (80 U ml–1) was continuously infused (25 µl h–1) in order to maintain catheter patency. The transducer was calibrated and connected to a computerized data acquisition system (BIOPAC System Inc. Goleta, CA, USA). Mice were allowed to recover for at least 7 days before any experiments were started. In considering that ingestion of water evokes pressor response and inhibits the release of VP, water and food were removed from the cages before experiments.
Experimental protocols
Experiment 1 was designed to investigate the effect of injection of hypertonic (HS) or isotonic saline (IS) into the carotid arterial catheter on BP and HR in AT1a–/– and+/+ mice. The procedures were: baseline BP recording (10 min); HS injection (20 µl, 20% NaCl) or IS injection (20 µl, 0.9% NaCl); and BP recording (10 min).
Experiment 2 was designed to investigate the effect of AT1 receptor blockade on HS-induced changes in BP and HR in AT1a–/– and+/+ mice. The procedures were: baseline BP recording (10 min); HS injection (20 µl, 20% NaCl) within 20 s; BP recording (10 min); losartan injection (20 mg kg–1, 20 µl) or sham injection (IS, 20 µl); 30 min interval; BP basal recording (10 min); HS injection (20 µl, 20% NaCl) within 20 s; and BP recording (10 min).
Experiment 3 was designed to investigate the effect of AT2 receptor blockade (PD123319, 15 mg kg–1, 20 µl) on HS-induced changes in BP and HR in AT1a–/– and+/+ mice. The procedures were similar to those described for Experiment 2.
Experiment 4 was designed to investigate the effect of HS injection on plasma osmolality and plasma VP concentration in AT1a–/– and+/+ mice. Blood samples (200 µl) were collected through the carotid arterial catheter into pre-cooled 1.5-ml tubes, before and immediately after (within 1 min) HS injection. The time point for the blood collection was determined on the basis of previous experiments (Chen et al. 2004a). Osmolality was measurement using 50 µl of the 200 µl collected blood sample. The remaining blood sample was centrifuged immediately and plasma was stored at –80°C for radioimmunoassay (RIA).
Experiment 5 was designed to investigate the effect of VP (5 ng g–1) injected into the carotid arterial catheter on BP and HR in AT1a–/– and+/+ mice. The procedures were: baseline BP recording (10 min); VP injection or control injection (0.9% NaCl); and BP recording (10 min).
Plasma osmolality was measured using freezing-point osmometry (Advanced Instruments Inc., Norwood, MA, USA). Plasma VP concentration was measured by RIA (Morris et al. 1999). Intra- and interassay variations were monitored to establish the continued reliability of the RIA procedure and antiserum. All samples from within an experiment were measured in the same assay to reduce variation.
The data are presented as means ± S.E.M. Comparisons between groups, treatments and time course were made in the acute osmotic stimulation study using a two or three-way ANOVA for analysis. One-way ANOVA was used for comparisons in the VP injection study. If a statistically significant effect was found, a Newman–Keuls test was performed to detect the difference between the groups. P < 0.05 was used as a criterion for significance.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
HS caused an increase in plasma osmolality with no difference noted between the groups. The elevated systemic osmolality induced a 2- to 4-fold increase in plasma VP concentration with similar responses between groups (Table 1).
|
AT1a–/– mice had a lower basal MAP than AT1a+/+ mice, with no difference in HR (Fig. 1). IS produced no effect on MAP or HR in either AT1a+/+ or AT1a–/– mice (data not shown). Acute intracarotid HS injection produced a rapid increase in MAP in both AT1a+/+ and AT1a–/– mice with a return to baseline within 10–15 min. HS induced a greater increase in MAP in AT1a–/– as compared to in AT1a+/+ mice (Tables 2 and 3, group effect, P = 0.02). The percentage increases of MAP 1, 5 and 10 min after HS injection were (AT1a–/– versus AT1a+/+, Fig. 2A): +28.1 ± 2.4% versus +15.5 ± 1.9% (P = 0.003), +23.7 ± 3.0% versus +13.7 ± 1.5% (P = 0.04) and +17.1 ± 3.9% versus +12.8 ± 1.8% (P = 0.052), respectively. There were no significant differences in HR (Figs 2B and 3B).
|
|
|
|
|
In order to determine whether Ang AT1b or AT2 receptors were involved in the control of basal BP and HR, we tested the effect of AT1 and AT2 receptor antagonists, losartan and PD123319, respectively. Results showed that the AT1 antagonist losartan did not alter basal MAP in AT1a+/+ or AT1a–/– mice (Fig. 1A). Likewise the AT2 antagonist, PD123319 treatment did not alter basal MAP in AT1a+/+ or AT1a–/– mice (Fig. 3A). Losartan and PD produced no effect on basal HR (Figs 1B and 3B).
Effect of pharmacological blockade of AT1 and AT2 receptors on the cardiovascular response to HS
In order to determine whether Ang AT1b or AT2 receptors were involved in the HS response, we tested the effect of AT1 and AT2 receptor antagonists, losartan and PD123319, respectively. To determine whether the second HS treatment may augment the BP response, we set saline injection for treatment controls in experiments 2 and 3. Results showed that the second injection of HS induced similar BP response as compared to the first HS injection in saline controls in AT1a+/+ and AT1a–/– mice (data not shown). Results showed that losartan blocked the higher MAP response in AT1a–/– mice, but not in AT1a+/+ mice (Table 2 and Fig. 2A). Losartan produced no effect on HR after osmotic stimulation (Fig. 2B). The AT2 antagonist, PD123319 did not inhibit the MAP response to osmotic stimulation (Table 3, Fig. 4A). The AT2 antagonist did not affect HR after HS injection (Fig. 4B).
|
In order to determine whether AT1a+/+ and AT1a–/– mice have a different pressor response to VP, we tested the effect of acute VP injection. Results showed that VP (5 ng g–1) induced an increase in MAP and HR in both groups with a maximum response seen in 1 min. There were no difference in maximum MAP and HR response to VP between AT1a+/+ and AT1a–/– mice (Table 4).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
To extend our studies of the role of AT1a receptors in osmosensitivity, we tested the effect of vascular injection of HS in AT1a–/– and+/+ mice. Using carotid arterial catheters, the objective was to directly and quickly stimulate brain osmoreceptors with similar increases in osmolality. The fact that the NaCl was injected into the carotid artery and that the pressure response occurs rapidly suggests that the pathway may be via the CNS. Results showed that HS produced a greater pressor response in AT1a–/– mice, indicating enhanced osmosensitivity. This supports other studies which showed enhanced responsiveness to more chronic osmotic stimuli (Oliverio et al. 2000a; Morris et al. 2001; Rocha et al. 2005). It is interesting that a model in which the renin–angiotensin system is over- rather then under-expressed in brain, the mRen2 transgenic rat, also showed an enhanced pressor response to osmotic stimuli (Nishioka et al. 1999). This result suggests a relationship between enhanced central angiotensinergic drive and central osmotic responses. However, from that study it is not clear whether the AT1a or AT1b receptor signals mediated the hypersensitivity. The difference may be related to the different route in which the osmotic stimulation was applied.
To evaluate whether AT1b or AT2 receptors are involved in the osmotic cascade, losartan (AT1 antagonist) or PD123319 (AT2 receptor antagonist) were used to block the AT1b (remaining AT1 receptors) or AT2 receptors in AT1a–/– mice. The results showed that acute blockade of AT1 or AT2 receptors had no effect on basal BP or HR in AT1a+/+ or AT1a–/– mice. A previous study had shown that chronic losartan treatment lowered BP in this strain (Oliverio et al. 1997). There is the possibility that losartan may have two different mechanisms (sites) of action in the two studies. It is possible that short-term use of losartan in the present study blocks AT1 receptors in the periphery, whereas losartan may act at both central and peripheral receptors when used for a longer duration in the study of Oliverio et al. (1997). Another major finding was that the enhanced HS pressor response in AT1a–/– mice was prevented by losartan, an effect which was not observed in the receptor-intact group. This may mean that the effect of HS in AT1a+/+ mice involves the central receptors and that in the AT1a–/– mice both central receptors and those accessed by circulating Ang II are involved. For example, there are AT1b receptors in SFO (Chen & Morris, 2001; Chen et al. 2003). This suggests that Ang AT1b receptors might be involved because losartan acts to inhibit the remaining AT1 signal (AT1b). A previous study had shown that AT1b mRNA is upregulated in the brainstem of AT1a–/– animals and in mice consuming a high-salt diet (Chen et al. 2002, 2004b). These data together suggest that the AT1b receptors are activated when the AT1a receptors are deleted, and this alteration in AT1b receptors may be responsible for the enhanced osmotic sensitivity. In contrast, PD123319 pretreatment did not antagonize the osmotic pressor responses in AT1a–/– and AT1a+/+ mice, suggesting that AT2 receptors did not play a role in the osmotic pressor response. There are several reports in rats that demonstrated the role for AT1 receptors in mediating osmotic responses (Chen & Toney, 2001; Zhang & Leenen, 2001). Losartan microinjected into bilateral PVN is reported to have no effect on resting renal sympathetic nerve activity (RSNA) but reduces RSNA response to HS (Chen & Toney, 2001). Peripheral administration of losartan can prevent the BP response induced by chronic central osmotic stimulation (Zhang & Leenen, 2001). A cellular osmosensitivity study in isolated supraoptic neurones using path-clamp electrophysiological recording provides direct evidence of the hyper-osmosensitivity in AT1a–/– mice (Skalska et al. 2005). The findings in this study deserve further exploration of its mechanisms. Using antisense oligonucleotides for the AT1 receptor suggested that the AT1 receptors in PVN mediated the salt-sensitive hypertension in mRen-2 transgenic rats (Li et al. 1996). Recently, we have developed RNA interference (RNAi) methods for silencing AT1a and AT1b receptors. Our study using adenovirus-mediated small hairpin RNA (shRNA) for site-specific silencing down AT1a receptors in mouse brain provides a new tool for this purpose (Chen et al. 2005). The data being collected by researchers using this new technique will help to further disclose the functions of these two receptor subtypes.
VP, a neuropeptide secreted from the neurohypophysis, is important in regulation of water balance and BP (Reghunandanan et al. 1991; Michelini & Morris, 1999; Oliverio et al. 2000a). Osmotic stimulation induces VP release and the pathway may involve central Ang receptors (Qadri et al. 1993; Bourque et al. 1994; Chen et al. 2004a). To determine whether VP plays a role in the altered pressor response, we measured HS-induced VP release in AT1a–/– and AT1 a+/+ mice. Data showed that the plasma VP levels were similar in both groups under basal and osmotically stimulated conditions. This suggests that VP does not mediate the enhanced BP response in AT1a–/– mice and indicates that AT1a receptors are not necessary to maintain osmotic control of VP release. In previous studies we showed a reduced plasma VP response to dehydration in AT1a–/– mice in association with an enhanced central neurosecretory response (Morris et al. 1999; 2001,). However, dehydration is a stimulus that produces both increased osmolality and hypovolaemia, which is different from the effect of acute HS injection. The interpretation of the plasma VP data must be tempered by results from our laboratory which show that the time course for neurosecretion in mice is extremely rapid (Chen et al. 2004a). The plasma VP response to systemic HS was almost instantaneous with a return to baseline levels within 1 min. This makes it difficult to say with certainty that there are not early changes in VP, not detected because of the experimental protocol. To determine whether altered response to VP accounts for the altered osmotic sensitivity, we measured the VP-induced pressor response in AT1a–/– and+/+ mice. The results showed that the VP-induced BP and HR responses were similar in AT1a–/– and AT1a+/+ mice. This observation did not support the possibility that the sensitivity of plasma VP mediates the osmotic hypersensitivity in AT1a–/– mice.
In summary, this study provides functional evidence that osmotic sensitivity is enhanced in animals lacking AT1a receptors. The mechanism of the changes may be related to activation of brain Ang AT1b receptors.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Bourque CW, Oliet SH & Richard D (1994). Osmoreceptors, osmoreception, and osmoregulation. Front Neuroendocrinol 15, 231–274.[CrossRef][Medline]
Burson JM, Aguilera G, Gross KW & Sigmund CD (1994). Differential expression of angiotensin receptor 1A and 1B in mouse. Am J Physiol 267, E260–E267.
Carlson SH, Beitz A & Osborn JW (1997). Intragastric hypertonic saline increases vasopressin and central Fos immunoreactivity in conscious rats. Am J Physiol 272, R750–R758.[Medline]
Chen Y, Da Rocha MJ & Morris M (2003). Osmotic regulation of angiotensin AT1 receptor subtypes in mouse brain. Brain Res 965, 35–44.[CrossRef][Medline]
Chen
Y
&
Morris
M (2001). Differentiation of brain angiotensin AT1a and AT1b receptor mRNAs: a specific effect of dehydration. Hypertension
37, 692–697.
Chen H, Morris M, Chen A & Chen Y (2005). In vivo study of adenovirus-small interference RNA: silencing AT1a receptors in mouse brain. FASEB J 19, A203.
Chen H, Morris M, Key MP & Chen Y (2004a). Rapid neurosecretory and cardiovascular response to osmotic stimulation in conscious mice. Neuroendocrinology 80, 225–232.[Medline]
Chen
QH
&
Toney
GM (2001). AT(1)-receptor blockade in the hypothalamic PVN reduces central hyperosmolality-induced renal sympathoexcitation. Am J Physiol Regul Integr Comp Physiol
281, R1844–R1853.
Chen Y, Oliveira G, Rocha MJA & Morris M (2002). Regulation of angiotensin AT1 mRNA in mouse brainstem: effects of dehydration and AT1a gene deletion. FASEB J 16, A571.
Chen Y, Liu-Stratton Y, Hassanain H, Cool D & Morris M (2004b). Dietary sodium regulates angiotensin AT1a and AT1b mRNA expression in mouse brain. Exp Neurol 188, 238–245.[CrossRef][Medline]
Davisson RL, Oliverio MI, Coffman TM & Sigmund CD (2000). Divergent functions of angiotensin II receptor isoforms in the brain. J Clin Invest 106, 103–106.[Medline]
De Gasparo
M, Catt
KJ, Inagami
T, Wright
JW
&
Unger
T (2000). International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev
52, 415–472.
Diz DI, Jessup JA, Westwood BM, Bosch SM, Vinsant S, Gallagher PE & Averill DB (2002). Angiotensin peptides as neurotransmitters/neuromodulators in the dorsomedial medulla. Clin Exp Pharmacol Physiol 29, 473–482.[CrossRef][Medline]
Fitzsimons
JT (1998). Angiotensin, thirst, and sodium appetite. Physiol Rev
78, 583–686.
Ito
M, Oliverio
MI, Mannon
PJ, Best
CF, Maeda
N, Smithies
O
&
Coffman
TM (1995). Regulation of blood pressure by the type 1A angiotensin II receptor gene. Proc Natl Acad Sci U S A
92, 3521–3525.
Joaquim
LF, Farah
VM, Bernatova
I, Fazan
RJR, Grubbs
R
&
Morris
M (2004). Enhanced heart rate variability and baroreflex index after stress and cholinesterase inhibition in mice. Am J Physiol Heart Circ Physiol
287, H251–H257.
Kakar SS, Riel KK & Neill JD (1992). Differential expression of angiotensin II receptor subtype mRNAs (AT-1A and AT-1B) in the brain. Biochem Biophys Res Commun 185, 688–692.[CrossRef][Medline]
Lazartigues
E, Dunlay
SM, Loihl
AK, Sinnayah
P, Lang
JA, Espelund
JJ, Sigmund
CD
&
Davisson
RL (2002). Brain-selective overexpression of angiotensin (AT1) receptors causes enhanced cardiovascular sensitivity in transgenic mice. Circ Res
90, 617–624.
Lenkei Z, Palkovits M, Corvol P & Llorens-Cortes C (1998). Distribution of angiotensin type-1 receptor messenger RNA expression in the adult rat brain. Neuroscience 82, 827–841.[CrossRef][Medline]
Li P, Morris M, Diz DI, Ferrario CM, Ganten D & Callahan MF (1996). Role of paraventricular angiotensin AT1 receptors in salt-sensitive hypertension in mRen-2 transgenic rats. Am J Physiol 270, R1178–R1181.
Li P, Sur SH, Mistlberger RE & Morris M (1999). Circadian blood pressure and heart rate rhythms in mice. Am J Physiol 276, R500–R504.
Michelini
LC
&
Morris
M (1999). Endogenous vasopressin modulates the cardiovascular responses to exercise. Ann N Y Acad Sci
897, 198–211.
Morris
M, Li
P, Callahan
MF, Oliverio
MI, Coffman
TM, Bosch
SM
&
Diz
DI (1999). Neuroendocrine effects of dehydration in mice lacking the angiotensin AT1a receptor. Hypertension
33, 482–486.
Morris
M, Means
S, Oliverio
MI
&
Coffman
TM (2001). Enhanced central response to dehydration in mice lacking angiotensin AT(1a) receptors. Am J Physiol Regul Integr Comp Physiol
280, R1177–R1184.
Nishioka
T, Callahan
MF, Li
P, Ferrario
CM, Ganten
D
&
Morris
M (1999). Increased central angiotensin and osmotic responses in the Ren-2 transgenic rat. Hypertension
33, 385–388.
Oliverio MI, Best CF, Kim HS, Arendshorst WJ, Smithies O & Coffman TM (1997). Angiotensin II responses in AT1A receptor-deficient mice: a role for AT1B receptors in blood pressure regulation. Am J Physiol 272, F515–F520.
Oliverio
MI, Best
CF, Smithies
O
&
Coffman
TM (2000a). Regulation of sodium balance and blood pressure by the AT(1A) receptor for angiotensin II. Hypertension
35, 550–554.
Oliverio
MI, Delnomdedieu
M, Best
CF, Li
P, Morris
M, Callahan
MF, Johnson
GA, Smithies
O
&
Coffman
TM (2000b). Abnormal water metabolism in mice lacking the type 1A receptor for ANG II. Am J Physiol Renal Physiol
278, F75–F82.
Oliverio
MI, Kim
HS, Ito
M, Le
T, Audoly
L, Best
CF, Hiller
S, Kluckman
K, Maeda
N, Smithies
O
&
Coffman
TM (1998). Reduced growth, abnormal kidney structure, and type 2 (AT2) angiotensin receptor-mediated blood pressure regulation in mice lacking both AT1A and AT1B receptors for angiotensin II. Proc Natl Acad Sci U S A
95, 15496–15501.
Phillips MI (1987). Functions of angiotensin in the central nervous system. Annu Rev Physiol 49, 413–435.[CrossRef][Medline]
Qadri
F, Culman
J, Veltmar
A, Maas
K, Rascher
W
&
Unger
T (1993). Angiotensin II-induced vasopressin release is mediated through alpha-1 adrenoceptors and angiotensin II AT1 receptors in the supraoptic nucleus. J Pharmacol Exp Ther
267, 567–574.
Reghunandanan V, Reghunandanan R & Marya RK (1991). Vasopressin: its possible role in circadian time keeping. Chronobiologia 18, 39–47.[Medline]
Rocha MJA, Chen Y, Oliveira GR & Morris M (2005). Physiological regulation of brain angiotensin AT1b mRNA in mice lacking AT1a receptors. Exp Neurol (in press).
Ruan
X, Oliverio
MI, Coffman
TM
&
Arendshorst
WJ (1999). Renal vascular reactivity in mice: AngII-induced vasoconstriction in AT1A receptor null mice. J Am Soc Nephrol
10, 2620–2630.
Skalska S, Morris M & Stern JE (2005). Enhanced cellular osmosensitivity of magnocellular neurosecretory neurons in mice lacking angiotensin AT1a receptors. FASEB J 19, A592.
Toney GM, Chen QH, Cato MJ & Stocker SD (2003). Central osmotic regulation of sympathetic nerve activity. Acta Physiol Scand 177, 43–55.[CrossRef][Medline]
Zhang
J
&
Leenen
FH (2001). AT(1) receptor blockers prevent sympathetic hyperactivity and hypertension by chronic ouabain and hypertonic saline. Am J Physiol Heart Circ Physiol
280, H1318–H1323.
Zhou
Y, Chen
Y, Dirksen
WP, Morris
M
&
Periasamy
M (2003). AT1b receptor predominantly mediates contractions in major mouse blood vessels. Circ Res
93, 1089–1094.
Zhou Y, Dirksen WP, Chen Y, Morris M, Periasamy M & Zweier JL (2005). A major role for angiotensin AT1b receptors in mouse mesenteric resistance vessels and its distribution in heart and neuroendocrine tissues. J Mol Cell Cardiol 38, 693–696.[CrossRef][Medline]
Zhu
Z, Zhang
SH, Wagner
C, Kurtz
A, Maeda
N, Coffman
TM
&
Arendshorst
WJ (1998). Angiotensin AT1B receptor mediates calcium signaling in vascular smooth muscle cells of AT1A receptor-deficient mice. Hypertension
31, 1171–1177.
|
Acknowledgements |
|---|
This article has been cited by other articles:
|
|
 |
|
  R. B. Wichi, V. Farah, Y. Chen, M. C. Irigoyen, and M. Morris Deficiency in angiotensin AT1a receptors prevents diabetes-induced hypertension Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2007; 292(3): R1184 - R1189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Chen, H. Chen, A. Hoffmann, D. R. Cool, D. I. Diz, M. C. Chappell, A. Chen, and M. Morris Adenovirus-Mediated Small-Interference RNA for In Vivo Silencing of Angiotensin AT1a Receptors in Mouse Brain Hypertension, February 1, 2006; 47(2): 230 - 237. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
