(Hypertension. 1996;28:153-158.)
© 1996 American Heart Association, Inc.
Articles |
Effects of Angiotensin II Infusion and Inhibition of Nitric Oxide Synthase on the Rat Aorta
the Department of Biochemistry and the Cardiovascular Institute, Boston (Mass) University School of Medicine.
Correspondence to Peter Brecher, PhD, Boston University School of Medicine, 80 E Concord St, Boston, MA 02118.
In previous studies, we showed that in vivo infusion of angiotensin II (Ang II) to adult rats induced vascular changes in gene expression, and this effect did not depend solely on blood pressure elevation. To determine whether nitric oxide can influence the effects of Ang II on the vessel wall, we administered to rats Ang II separately or in combination with the arginine analogue N
-nitro-L-arginine methyl ester, which inhibits nitric oxide synthase chronically when given in vivo. We measured changes in aortic medial thickness, the association of macrophages with the endothelial surface of the aorta, the presence of proliferating cell nuclear antigen in the intima and adventitia as an index of aortic cell cycle changes, and the expression of immunodetectable fibronectin as an index of changes in the extracellular matrix. After 18 days of nitric oxide inhibition, the major changes were increased medial thickness and a 3.5-fold increase in the number of adherent macrophages. Rats treated with two different doses of Ang II for 3 days had a fivefold and threefold increase in the number of proliferating cells from the intimal and adventitial regions, respectively. Combined treatment resulted in increased medial thickness, intimal and adventitial cell proliferation, and macrophage adherence. An increased and altered pattern of fibronectin distribution was found in all treatment groups. Losartan administration prevented the effects of Ang II but not of nitric oxide inhibition, whereas administration of L-arginine prevented both intimal macrophage adherence and increased adventitial proliferation in rats given combined treatment. The data suggest that nitric oxide selectively influences macrophage association with the arterial wall, whereas Ang II and nitric oxide may have opposing effects on arterial cell proliferation.
Key Words: angiotensin II • nitric oxide • rats • aorta • hypertension, experimental • immunohistochemistry
This article has been cited by other articles:
 |
|
 |
|
  C. Bouvet, L.-A. Gilbert, D. Girardot, D. deBlois, and P. Moreau Different Involvement of Extracellular Matrix Components in Small and Large Arteries During Chronic NO Synthase Inhibition Hypertension, March 1, 2005; 45(3): 432 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Higashi, H. Shimokawa, T. Hattori, J. Hiroki, Y. Mukai, K. Morikawa, T. Ichiki, S. Takahashi, and A. Takeshita Long-Term Inhibition of Rho-Kinase Suppresses Angiotensin II-Induced Cardiovascular Hypertrophy in Rats In Vivo: Effect on Endothelial NAD(P)H Oxidase System Circ. Res., October 17, 2003; 93(8): 767 - 775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Haider, I. Lee, J. Grabarek, Z. Darzynkiewicz, and N. R. Ferreri Dual Functionality of Cyclooxygenase-2 as a Regulator of Tumor Necrosis Factor-Mediated G1 Shortening and Nitric Oxide-Mediated Inhibition of Vascular Smooth Muscle Cell Proliferation Circulation, August 26, 2003; 108(8): 1015 - 1021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. M.A.C. Martens, B. Demeilliers, D. Girardot, C. Daigle, H. H. Dao, D. deBlois, and P. Moreau Vessel-Specific Stimulation of Protein Synthesis by Nitric Oxide Synthase Inhibition: Role of Extracellular Signal-Regulated Kinases 1/2 Hypertension, January 1, 2002; 39(1): 16 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Osanai, N. Akutsu, N. Fujita, T. Nakano, K. Takahashi, W. Guan, and K. Okumura Cross talk between prostacyclin and nitric oxide under shear in smooth muscle cell: role in monocyte adhesion Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H177 - H182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Gu, J. Lynch, and P. Brecher Nitric Oxide Increases p21Waf1/Cip1 Expression by a cGMP-dependent Pathway That Includes Activation of Extracellular Signal-regulated Kinase and p70S6k J. Biol. Chem., April 6, 2000; 275(15): 11389 - 11396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Usui, K. Egashira, H. Tomita, M. Koyanagi, M. Katoh, H. Shimokawa, M. Takeya, T. Yoshimura, K. Matsushima, and A. Takeshita Important Role of Local Angiotensin II Activity Mediated via Type 1 Receptor in the Pathogenesis of Cardiovascular Inflammatory Changes Induced by Chronic Blockade of Nitric Oxide Synthesis in Rats Circulation, January 25, 2000; 101(3): 305 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Gu and P. Brecher Nitric Oxide-Induced Increase in p21Sdi1/Cip1/Waf1 Expression During the Cell Cycle in Aortic Adventitial Fibroblasts Arterioscler Thromb Vasc Biol, January 1, 2000; 20(1): 27 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Osanai, N. Fujita, N. Fujiwara, T. Nakano, K. Takahashi, W. Guan, and K. Okumura Cross talk of shear-induced production of prostacyclin and nitric oxide in endothelial cells Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H233 - H238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Usui, K. Egashira, S. Kitamoto, M. Koyanagi, M. Katoh, C. Kataoka, H. Shimokawa, and A. Takeshita Pathogenic Role of Oxidative Stress in Vascular Angiotensin-Converting Enzyme Activation in Long-Term Blockade of Nitric Oxide Synthesis in Rats Hypertension, October 1, 1999; 34(4): 546 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Cao, R. Dean, L. Wu, D. Casley, and M. E. Cooper Role of Angiotensin Receptor Subtypes in Mesenteric Vascular Proliferation and Hypertrophy Hypertension, September 1, 1999; 34(3): 408 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-A. Haefliger, P. Meda, A. Formenton, P. Wiesel, A. Zanchi, H. R. Brunner, P. Nicod, and D. Hayoz Aortic Connexin43 Is Decreased During Hypertension Induced by Inhibition of Nitric Oxide Synthase Arterioscler Thromb Vasc Biol, July 1, 1999; 19(7): 1615 - 1622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nicoletti and J.-B. Michel Cardiac fibrosis and inflammation: interaction with hemodynamic and hormonal factors Cardiovasc Res, March 1, 1999; 41(3): 532 - 543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gollasch, G. C. Wellman, H. J. Knot, J. H. Jaggar, D. H. Damon, A. D. Bonev, and M. T. Nelson Ontogeny of Local Sarcoplasmic Reticulum Ca2+ Signals in Cerebral Arteries : Ca2+ Sparks as Elementary Physiological Events Circ. Res., November 30, 1998; 83(11): 1104 - 1114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Katoh, K. Egashira, M. Usui, T. Ichiki, H. Tomita, H. Shimokawa, H. Rakugi, and A. Takeshita Cardiac Angiotensin II Receptors Are Upregulated by Long-Term Inhibition of Nitric Oxide Synthesis in Rats Circ. Res., October 5, 1998; 83(7): 743 - 751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Luvara, M. E. Pueyo, M. Philippe, C. Mandet, F. Savoie, D. Henrion, and J.-B. Michel Chronic Blockade of NO Synthase Activity Induces a Proinflammatory Phenotype in the Arterial Wall : Prevention by Angiotensin II Antagonism Arterioscler Thromb Vasc Biol, September 1, 1998; 18(9): 1408 - 1416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Parker, S. S. Wade, and R. L. Prewitt Pressure Mediates Angiotensin II–Induced Arterial Hypertrophy and PDGF-A Expression Hypertension, September 1, 1998; 32(3): 452 - 458. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Moreau, H. Takase, L. V. d'Uscio, T. F. Luscher, and G. L. Baumbach Effect of Chronic Nitric Oxide Deficiency on Angiotensin II–Induced Hypertrophy of Rat Basilar Artery • Editorial Comment Stroke, May 1, 1998; 29(5): 1031 - 1036. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Pagano, J. K. Clark, M. E. Cifuentes-Pagano, S. M. Clark, G. M. Callis, and M. T. Quinn Localization of a constitutively active, phagocyte-like NADPH oxidase in rabbit aortic adventitia: Enhancement by angiotensin II PNAS, December 23, 1997; 94(26): 14483 - 14488. [Abstract] [Full Text] [PDF]
|
|