Published online before print November 7, 2002, doi: 10.1161/01.RES.0000046018.23605.3E
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on August 8, 2002
Revised on October 2, 2002
Accepted on October 29, 2002
Estrogens Inhibit Angiotensin II-Induced Leukocyte-Endothelial Cell Interactions In Vivo via Rapid Endothelial Nitric Oxide Synthase and Cyclooxygenase Activation
Ángeles Álvarez ;
From the Department of Pharmacology (A.A., J.V.E., M.-J.S.), Faculty of Medicine, and Research Unit (C.H.), Clinic Hospital, University of Valencia, Spain, and Departments of Pediatrics, Pathology, Microbiology, and Immunology (A.C.I.), Dalhousie University, Halifax, Nova Scotia, Canada.
* To whom correspondence should be addressed. E-mail: maria.j.sanz{at}uv.es.
Angiotensin II (Ang II) may be a key molecule in the development of atherosclerosis. Because the incidence of coronary atherosclerosis in premenopausal women is lower than that observed in men or postmenopausal women, we have investigated the effect of estrogens on Ang II-induced leukocyte recruitment in vivo using intravital microscopy in the rat mesenteric microcirculation. Superfusion for 60 minutes with Ang II induced a significant increase in leukocyte rolling flux, adhesion, and emigration. Administration of 17-
-estradiol (17--E) after 30 minutes of Ang II superfusion produced a reduction of these leukocyte responses by 55.1%, 72.7%, and 70.9%, respectively, an additional 30 minutes later. The effect observed with 17--E was receptor-mediated and specific. 17--E superfusion did not modify either L-NAME or indomethacin-induced leukocyte responses. Inhibitory responses caused by 17--E were not altered by either 7-nitroindazole or actinomycin D cosuperfusion. Stimulation of endothelial cells with 17--E caused a rapid and dose-dependent release of prostacyclin. Finally, tamoxifen or ICI 182,780 administration provoked a significant increase in leukocyte-endothelial cell interactions 90 minutes later, which were significantly attenuated by systemic preadministration with an Ang II AT1 receptor antagonist. Tamoxifen-induced leukocyte responses were also reduced by systemic pretreatment with an anti-P-selectin mAb and an anti-CD18 mAb. Hence, the antiatherogenic effects of estrogens may be mediated by inhibition of Ang II-induced leukocyte recruitment through endothelial NO and prostacyclin release. Furthermore, scarcity of estrogens resulted in decreased levels of vasodilators and the exposure of the endothelium to the deleterious action of Ang II, which may explain the higher incidence of coronary atherosclerosis in men and postmenopausal women.
Key words: leukocytes • endothelium • cell adhesion molecules • intravital microscopy • prostacyclin
This article has been cited by other articles:
 |
|
 |
|
  M. Abu-Taha, C. Rius, C. Hermenegildo, I. Noguera, J.-M. Cerda-Nicolas, A. C. Issekutz, P. J. Jose, J. Cortijo, E. J. Morcillo, and M.-J. Sanz Menopause and Ovariectomy Cause a Low Grade of Systemic Inflammation that May Be Prevented by Chronic Treatment with Low Doses of Estrogen or Losartan J. Immunol., July 15, 2009; 183(2): 1393 - 1402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. Yanes, J. C. Sartori-Valinotti, and J. F. Reckelhoff Sex Steroids and Renal Disease: Lessons From Animal Studies Hypertension, April 1, 2008; 51(4): 976 - 981. [Full Text] [PDF]
|
|
|
|
|
|
S. Hagita, M. Osaka, K. Shimokado, and M. Yoshida Oxidative Stress in Mononuclear Cells Plays a Dominant Role in Their Adhesion to Mouse Femoral Artery After Injury Hypertension, March 1, 2008; 51(3): 797 - 802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Alvarez, M. S. Ibiza, M. M. Andrade, A. Blas-Garcia, and S. Calatayud Gastric Antisecretory Drugs Induce Leukocyte-Endothelial Cell Interactions through Gastrin Release and Activation of CCK-2 Receptors J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 406 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Toda, K. Ayajiki, and T. Okamura Interaction of Endothelial Nitric Oxide and Angiotensin in the Circulation Pharmacol. Rev., March 1, 2007; 59(1): 54 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Alvarez, S. Ibiza, C. Hernandez, A. Alvarez-Barrientos, J. V. Esplugues, and S. Calatayud Gastrin induces leukocyte-endothelial cell interactions in vivo and contributes to the inflammation caused by Helicobacter pylori FASEB J, November 1, 2006; 20(13): 2396 - 2398. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Park, J. I. Kim, Y. Ahn, A. J. Bonventre, and J. V. Bonventre Testosterone Is Responsible for Enhanced Susceptibility of Males to Ischemic Renal Injury J. Biol. Chem., December 10, 2004; 279(50): 52282 - 52292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Xing, A. Miller, L. Novak, R. Rocha, Y.-F. Chen, and S. Oparil Estradiol and Progestins Differentially Modulate Leukocyte Infiltration After Vascular Injury Circulation, January 20, 2004; 109(2): 234 - 241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Garbe and S. Suissa Issues to debate on the Women's Health Initiative (WHI) study: Hormone replacement therapy and acute coronary outcomes: methodological issues between randomized and observational studies Hum. Reprod., January 1, 2004; 19(1): 8 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Martin-McNulty, D. M. Tham, V. da Cunha, J. J. Ho, D. W. Wilson, J. C. Rutledge, G. G. Deng, R. Vergona, M. E. Sullivan, and Y.-X. Wang 17{beta}-Estradiol Attenuates Development of Angiotensin II-Induced Aortic Abdominal Aneurysm in Apolipoprotein E-Deficient Mice Arterioscler Thromb Vasc Biol, September 1, 2003; 23(9): 1627 - 1632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bregonzio, I. Armando, H. Ando, M. Jezova, G. Baiardi, and J. M. Saavedra Anti-inflammatory effects of angiotensin II AT1 receptor antagonism prevent stress-induced gastric injury Am J Physiol Gastrointest Liver Physiol, July 7, 2003; 285(2): G414 - G423. [Abstract] [Full Text] [PDF]
|
|