Angiotensin II (ANG II) is known to be a potent growth promoting factor for vascular smooth muscle cells and fibroblasts but little is known about its influence on growth in endothelial cells. We studied the effects of ANG II on endothelial growth and the role of the angiotensin receptor subtypes involved. Proliferation of rat coronary endothelial cells (CEC) and rat vascular smooth muscle cells (VSMC) was determined by [3H]thymidine incorporation, the MTT-test and by directly counting cells in a coulter counter. Angiotensin AT1- and AT2-receptors were demonstrated by binding studies and by the presence of their respective mRNA through reverse transcription polymerase chain reaction (RT-PCR). In contrast to VSMC, which in culture only express the AT1-receptor, CEC express both, AT1- and AT2-receptors simultaneously up to the third passage. Whereas ANG II stimulated growth of quiescent VSMC, an effect abolished by pretreatment with the AT1-receptor antagonist, losartan, ANG II did not induce proliferation in quiescent CEC. However, after pretreatment of quiescent endothelial cells (< passage 4) with the AT2-receptor antagonist, PD 123177, ANG II induced proliferation. This effect was reversed by additional pretreatment with losartan. ANG II significantly inhibited the proliferation of bFGF-stimulated CEC in a dose-dependent manner by maximally 50%. This effect was prevented by PD 123177 while losartan was ineffective. The AT2-receptor agonist, CGP 42112, mimicked the antiproliferative actions of ANG II, confirming the specificity of the effect. Our results show that the growth modulating actions of ANG II depend on the type of angiotensin receptor present on a given cell. In coronary endothelial cells, the antiproliferative actions of the AT2-receptor offset the growth promoting effects mediated by the AT1-receptor.
M Stoll, U M Steckelings, M Paul, S P Bottari, R Metzger, T Unger
Title and authors | Publication | Year |
---|---|---|
Involvement of alpha3 integrin/tetraspanin complexes in the angiogenic response induced by angiotensin II
C Domínguez-Jiménez, M Yáñez-Mó, A Carreira, R Tejedor, R González-Amaro, V Alvarez, F Sánchez-Madrid |
The FASEB Journal | 2001 |
Two Distinct Mechanisms of Angiotensin II-Induced Negative Regulation of the Mitogen-Activated Protein Kinases in Cultured Cardiac Myocytes
Y HIROI, J HIROI, S KUDOH, Y YAZAKI, R NAGAI, I KOMURO |
Hypertension Research | 2001 |
Protection against ischemia: a physiological function of the renin-angiotensin system
J Achard |
Biochemical Pharmacology | 2001 |
Differential effects of angiotensin AT1 and AT2 receptors on the expression, translation and function of the Na+-H+ exchanger and Na+-HCO3− symporter in the rat heart after myocardial infarction
S Sandmann, M Yu, E Kaschina, A Blume, E Bouzinova, C Aalkjaer, T Unger |
Journal of the American College of Cardiology | 2001 |
Transcriptional and translational regulation of calpain in the rat heart after myocardial infarction - effects of AT1and AT2receptor antagonists and ACE inhibitor
S Sandmann, M Yu, T Unger |
British Journal of Pharmacology | 2001 |
Effects of TCV-116 on expression of NOS and adrenomedullin in failing heart of Dahl salt-sensitive rats
N Kobayashi |
Atherosclerosis | 2001 |
Irbesartan, an angiotensin type 1 receptor inhibitor, regulates the vascular oxidative state in patients with coronary artery disease
BV Khan, S Navalkar, QA Khan, ST Rahman, S Parthasarathy |
Journal of the American College of Cardiology | 2001 |
Vascular expression of angiotensin type 2 receptor in the adult rat: influence of angiotensin II infusion
F Bonnet, ME Cooper, RM Carey, D Casley, Z Cao |
Journal of Hypertension | 2001 |
Effects of antihypertensive drugs on vascular remodeling: do they predict outcome in response to antihypertensive therapy?
EL Schiffrin |
Current Opinion in Nephrology and Hypertension | 2001 |
Differences between Squamous Cell Carcinoma and Keratoacanthoma in Angiotensin Type-1 Receptor Expression
H Takeda, S Kondo |
The American Journal of Pathology | 2001 |
Interactions of Ligands at Angiotensin II-Receptors and Imidazoline Receptors
U Wethmar, W Raasch, A Dendorfer, P Dominiak |
The Japanese Journal of Pharmacology | 2001 |
Role Of Angiotensin Type 2 Receptors In Human Forearm Vascular Responses Of Normal Volunteers
S Phoon, LG Howes |
Clinical and Experimental Pharmacology and Physiology | 2001 |
Immunohistochemical study of angiotensin receptors in normal human sweat glands and eccrine poroma
H Takeda, S Kondo |
British Journal of Dermatology | 2001 |
Coronary Capillary Remodeling in Non-Insulin-Dependent Diabetic Rats: Amelioration by Inhibition of Angiotensin Converting Enzyme and Its Potential Clinical Implications
T SUGAWARA, S FUJII, AK Tarikuz, D GOTO, T KANEKO, T FURUMOTO, H TOGASHI, M YOSHIOKA, T KOYAMA, A KITABATAKE |
Hypertension Research | 2001 |
Angiotensin II type 2 receptors: signalling and pathophysiological role
A Blume, E Kaschina, T Unger |
Current Opinion in Nephrology and Hypertension | 2001 |
AT1 receptor is present in glioma cells; its blockage reduces the growth of rat glioma
E Rivera, O Arrieta, P Guevara, A Duarte-Rojo, J Sotelo |
British Journal of Cancer | 2001 |
Role of the angiotensin II receptor blocker valsartan in heart failure
RL Webb, M Gasparo |
Experimental and clinical cardiology | 2001 |
Effect of Angiotensin II Type 2 Receptor on Tyrosine Kinase Pyk2 and c-Jun NH2-Terminal Kinase via SHP-1 Tyrosine Phosphatase Activity: Evidence from Vascular-Targeted Transgenic Mice of AT2 Receptor
H Matsubara, Y Shibasaki, M Okigaki, Y Mori, H Masaki, A Kosaki, Y Tsutsumi, Y Uchiyama, S Fujiyama, A Nose, O Iba, E Tateishi, T Hasegawa, M Horiuchi, C Nahmias, T Iwasaka |
Biochemical and Biophysical Research Communications | 2001 |
Role of Asp297 of the AT2 receptor in high-affinity binding to different peptide ligands
D Knowle, J Kurfis, N Gavini, L Pulakat |
Peptides | 2001 |
Differential Activation of the STAT Pathway by Angiotensin II via Angiotensin Type 1 and Type 2 Receptors in Cultured Human Fetal Mesangial Cells
FA Seebach, T Welte, XY Fu, LH Block, M Kashgarian |
Experimental and Molecular Pathology | 2001 |
Attenuation of angiotensin II-mediated coronary vasoconstriction and vasodilatory action of angiotensin-converting enzyme inhibitor in pacing-induced heart failure in dogs
Y Oikawa, K Maehara, T Saito, K Tamagawa, Y Maruyama |
Journal of the American College of Cardiology | 2001 |
Transgenic mouse models of angiotensin receptor subtype function in the cardiovascular system
M Brede, L Hein |
Regulatory Peptides | 2001 |
Angiotensin and its AT2 receptor: new insights into an old system
M Stoll, T Unger |
Regulatory Peptides | 2001 |
Opposite regulation of brain angiotensin type 1 and type 2 receptors in cold-induced hypertension
JF Peng, MI Phillips |
Regulatory Peptides | 2001 |
Heart Physiology and Pathophysiology
NS Dhalla, RM Temsah, T Netticadan, MS Sandhu |
Heart Physiology and Pathophysiology | 2001 |
Angiotensin II type 1 receptor expression in human pancreatic cancer and growth inhibition by angiotensin II type 1 receptor antagonist
Y Fujimoto, T Sasaki, A Tsuchida, K Chayama |
FEBS Letters | 2001 |
Angiotensin II type 1 receptor blockers
M Burnier |
Circulation | 2001 |
Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide
H Gavras, HR Brunner |
American journal of physiology. Heart and circulatory physiology | 2001 |
Selective inhibition of the renal angiotensin type 2 receptor increases blood pressure in conscious rats
AF Moore, NT Heiderstadt, E Huang, NL Howell, ZQ Wang, HM Siragy, RM Carey |
Hypertension | 2001 |
Angiotensin II type 2 receptor inhibits epidermal growth factor receptor transactivation by increasing association of SHP-1 tyrosine phosphatase
Y Shibasaki, H Matsubara, Y Nozawa, Y Mori, H Masaki, A Kosaki, Y Tsutsumi, Y Uchiyama, S Fujiyama, A Nose, O Iba, E Tateishi, T Hasegawa, M Horiuchi, C Nahmias, T Iwasaka |
Hypertension | 2001 |
Angiotensin II Binding Sites in the Heart of Scyliorhinus canicula: An Autoradiographic Study
MC Cerra, ML Tierney, Y Takei, N Hazon, B Tota |
General and Comparative Endocrinology | 2001 |
Myocardial Ischemia Activates the JAK–STAT Pathway Through Angiotensin II Signaling in in vivo Myocardium of Rats
T Omura, M Yoshiyama, F Ishikura, H Kobayashi, K Takeuchi, S Beppu, J Yoshikawa |
Journal of Molecular and Cellular Cardiology | 2001 |
Angiotensin Blockade Inhibits Increased JNKs, AP-1 and NF- κ B DNA-binding Activities in Myocardial Infarcted Rats
M Yoshiyama, T Omura, K Takeuchi, S Kim, K Shimada, H Yamagishi, M Teragaki, K Akioka, H Iwao, J Yoshikawa |
Journal of Molecular and Cellular Cardiology | 2001 |
AT RECEPTOR INHIBITION AFFECTS THE NORADRENALINE SENSITIVITY IN ISOLATED PORTAL VEIN OF NORMOTENSIVE RAT
JY Datté, JY Datté, P Gohlke, C Pees, A Ziegler |
Clinical and Experimental Hypertension | 2001 |
Expanded role for ARBs in cardiovascular and renal disease?: Recent observations have far-reaching implications
TM Ramahi |
Postgraduate Medicine | 2001 |
Addressing Those Two That Go Together: The Angiotensin II Receptors and their Role in Blood-flow Regulation
R Fogari, MD Gasparo |
Blood Pressure | 2001 |
Small Artery Remodeling in Hypertension: Can It Be Corrected?
MA Moore, EL Schiffrin |
The American Journal of the Medical Sciences | 2001 |
AT 2 receptor-mediated vasodilation in the heart: effect of myocardial infarction
MP Schuijt, M Basdew, R Veghel, R Vries, PR Saxena, RG Schoemaker, AH Danser |
American journal of physiology. Heart and circulatory physiology | 2001 |
Angiotensin II AT 2 receptors inhibit growth responses in proximal tubule cells
J Zimpelmann, KD Burns |
American journal of physiology. Renal physiology | 2001 |
Comparative Effects of ACE Inhibitors and an Angiotensin Receptor Blocker on Atherosclerosis and Vascular Function
Y Sun, B Zhu, AE Browne, S Pulukurthy, TM Chou, K Sudhir, SA Glantz, PC Deedwania, K Chatterjee, WW Parmley |
Journal of cardiovascular pharmacology and therapeutics | 2001 |
ANG II potentiates mitogenic effect of norepinephrine in vascular muscle cells: role of FGF-2
A Parenti, L Brogelli, S Donnini, M Ziche, F Ledda |
American journal of physiology. Heart and circulatory physiology | 2001 |
Review: AT 1-receptor blockade in experimental myocardial ischaemia/reperfusion
R Schulz, G Heusch |
Journal of Renin-Angiotensin-Aldosterone System | 2001 |
Review: AT1-receptors in the central nervous system
AM Allen, ME Giles, JH Lee, BJ Oldfield, FA Mendelsohn, MJ McKinley |
Journal of Renin-Angiotensin-Aldosterone System | 2001 |
Vascular Hypertrophy and Increased P70S6 Kinase in Mice Lacking the Angiotensin II AT 2 Receptor
M Brede, K Hadamek, L Meinel, F Wiesmann, J Peters, S Engelhardt, A Simm, A Haase, MJ Lohse, L Hein |
Circulation | 2001 |
Angiotensin AT 1 and AT 2 Receptors Differentially Regulate Angiopoietin-2 and Vascular Endothelial Growth Factor Expression and Angiogenesis by Modulating Heparin Binding–Epidermal Growth Factor (EGF)–Mediated EGF Receptor Transactivation
S Fujiyama, H Matsubara, Y Nozawa, K Maruyama, Y Mori, Y Tsutsumi, H Masaki, Y Uchiyama, Y Koyama, A Nose, O Iba, E Tateishi, N Ogata, N Jyo, S Higashiyama, T Iwasaka |
Circulation research | 2001 |
Apoptosis Is Not Increased in Myocardium Overexpressing Type 2 Angiotensin II Receptor in Transgenic Mice
H Sugino, R Ozono, S Kurisu, H Matsuura, M Ishida, T Oshima, M Kambe, Y Teranishi, H Masaki, H Matsubara |
Hypertension | 2001 |
Coronary Hemodynamic and Ventricular Responses to Angiotensin Type 1 Receptor Inhibition in SHR: Interaction With Angiotensin Type 2 Receptors
J Varagic, D Susic, ED Frohlich |
Hypertension | 2001 |
Enhanced Angiotensin II Activity in Heart Failure: Reevaluation of the Counterregulatory Hypothesis of Receptor Subtypes
LH Opie, MN Sack |
Circulation research | 2001 |
Workshop: Hypertension and Cardiovascular Risk Factors: Role of the Angiotensin II–Nitric Oxide Interaction
L Raij |
Hypertension | 2001 |
Angiotensin Type 1 Receptor Antagonism and ACE Inhibition Produce Similar Renoprotection in Nω -Nitro- l >-Arginine Methyl Ester/Spontaneously Hypertensive Rats
Y Nakamura, H Ono, X Zhou, ED Frohlich |
Hypertension | 2001 |
Blockade of Angiotensin Receptor Subtypes in Arcuate Uterine Artery of Pregnant and Postpartum Rats
J St-Louis, B Sicotte, S Bédard, M Brochu |
Hypertension | 2001 |
Activation of Angiotensin II Subtype 2 Receptor Induces Catecholamine Release in an Extracellular Ca2+-Dependent Manner through a Decrease of Cyclic Guanosine 3′,5′-Monophosphate Production in Cultured Porcine Adrenal Medullary Chromaffin Cells*
K Takekoshi, K Ishii, Y Kawakami, K Isobe, T Nakai |
Endocrinology | 2001 |
Klinische Diabetologie
BO Böhm, KD Palitzsch, C Rosak, GA Spinas |
2001 | |
Chimeric AT 1 /AT 2 Receptors Reveal Functional Similarities Despite Key Amino Acid Dissimilarities in the Domains Mediating Agonist-Dependent Activation
J Hines, SJ Fluharty, DK Yee |
Biochemistry | 2001 |