Abstract: Angiotensin II (ANG II) produces vasoconstriction by a direct action on smooth muscle cells via AT 1 receptors. These receptors are also present in the endothelium, but their function is poorly understood. This study was therefore undertaken to determine whether ANG II elicits the release of nitric oxide (NO) from cultured rat aortic endothelial cells. NO production, measured by the accumulation of nitrite and nitrate, was enhanced by 10 −7 M ANG II. The biological activity of the NO released by ANG II action was evaluated by measuring its guanylate cyclase-stimulating activity in smooth muscle cells. The guanosine 3′,5′-cyclic monophosphate (cGMP) content of smooth muscle cells was significantly increased by exposure of supernatant from ANG II-stimulated endothelial cells. These effects resulted from the activation of NO synthase, as they were inhibited by the l-arginine analogs. These ANG II actions were mediated by the AT 1 receptor, as shown by their inhibition by the AT 1 antagonist losartan. The cGMP production by reporter cells was inhibited by the calmodulin antagonist W-7, suggesting that ANG II activates endothelial calmodulin-dependent NO synthase. This hypothesis is also supported by the increase of intracellular free calcium induced by ANG II in endothelial cells. ANG II also stimulated luminol-enhanced chemiluminescence in endothelial cells. This effect was inhibited by N ω -monomethyl-l-arginine and superoxide dismutase, suggesting that this luminol-enhanced chemiluminescence reflected an increase in peroxynitrite production. Thus ANG II stimulates NO release from macrovascular endothelium, which may modulate the direct vasoconstrictor effect of ANG II on smooth muscle cells. However, this beneficial effect may be counteracted by the simultaneous production of peroxynitrite, which could contribute to several pathological processes in the vascular wall.

Abstract: Physiological adaptation of normal blood vessels to acute or chronic changes in blood flow is endothelium dependent. In vitro studies have shown that, among other genes, NO synthase (NOS) 3 mRNA and protein expression is enhanced by acute elevation of shear stress in endothelial cells. We have investigated the effect of chronic high blood flow on NOS3 mRNA and protein expression in rat aorta. NOS3 mRNA levels were measured by quantitative polymerase chain reaction (PCR) in the aortas of 12 rats with arteriovenous fistulas and 9 sham-operated control rats. The PCR assay indicated that NOS3 mRNA levels were significantly enhanced (twofold) during high blood flow. Western blots showed that immunoreactive NOS3 levels were also increased to a similar extent. Furthermore, the Ca 2+ -dependent NOS activity, measured by the l -arginine to l -citrulline conversion assay, and the cGMP content were also significantly increased in the proximal aortic wall submitted to the arteriovenous shunt. These results indicate that NOS3 mRNA and protein expression is enhanced in vivo during chronic high blood flow.

Abstract: Oxidized LDLs are thought to play a central role in atherogenesis. Among their wide variety of biological properties, oxidized LDLs exhibit a cytotoxic effect on cultured vascular cells. Toxic doses of mildly oxidized LDLs elicited massive apoptosis in both primary and immortalized cultures of endothelial cells as shown by characteristic morphological and biochemical changes. Cytoplasmic and nucleic modifications (eg, chromatin condensation and nucleus fragmentation) were visualized by using electron and fluorescence microscopy of intact cells labeled by the fluorescent DNA probe SYTO-11. DNA fragmentation was quantified by ultracentrifugation of chromatin fragments, evaluated in situ by using the TUNEL ( T erminal transferase-mediated d U TP-biotin n ick e nd l abeling) procedure, and visualized by electrophoresis of radiolabeled DNA fragments showing the characteristic apoptotic ladder. Apoptotic cells became rapidly detached and underwent postapoptotic necrosis that led to cell disintegration. Apoptosis was subsequent to a sustained and delayed peak of cytosolic calcium. Both the calcium peak and apoptosis were blocked by chelating the extracellular calcium with EGTA or by inhibiting the calcium influx by the calcium-channel blockers nifedipine and nisoldipine, thus suggesting that the apoptotic process induced by oxidized LDLs is clearly calcium dependent. Aurintricarboxylic acid, an inhibitor of endonucleases, also blocked the apoptotic process without blocking the calcium peak. These results suggest that toxic doses of mildly oxidized LDLs induce massive apoptosis of endothelial cells through a calcium-dependent mechanism and that this apoptotic process can be prevented by inhibiting the rise of cytosolic calcium or by inhibiting cellular endonucleases by aurintricarboxylic acid.

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Weems, Battered Love: Marriage, Sex, and Violence in the Hebrew Prophets, reviewed by John L. McLaughlin Brad H. Young, Jesus the Jewish Theologian, reviewed by Robert Derrenbacker John M. Badertscher, Gordon Harland and Roland E. Miller, Religious Studies in Manitoba and Saskatchewan: A State-of-the-Art Review, reviewed by Bryan Hills Brian J. Fraser, The Study of Religion in British Columbia: A State-of-the-Art Review, reviewed by Robert K. Burkinshaw R.D. Gidney and W.P.I. Millar, Professional Gentlemen: The Professions in Nineteenth-Century Ontario, reviewed by Sharon Anne Cook Carmel McEnroy, Guests in Their Own House: The Women of Vatican II., reviewed by Ellen M. Leonard Mark A. Noll, David W. Bebbington and George A. Rawlyk, eds., Evangelicalism: Comparative Studies in Popular Protestantism in North America. the British Isles, and Beyond 1700-1990, reviewed by John W. Stephenson Elizabeth Alvilda Petroff, Body and Soul: Essays on Medieval Women and Mysticism, reviewed by Kate Galea Kim Power, Veiled Desire: Augustine on Women, reviewed by Richard Valantasis Scott L. Waugh and Peter D. Diehl, eds., Christendom and Its Discontents: Exclusion, Persecution, and Rebellion 1000-1500, reviewed by Evelyn A. Mackie Earle H. Waugh, Dissonant Worlds: Roger Vandersteene Among the Cree, reviewed by David Nazar Peter Wyatt, Jesus Christ and Creation in· the Theology of John Calvin, reviewed by Anna Case-Winters John Fenwick and Bryan Spinks, Worship in Transition: The Liturgical Movement in the Twentieth Century, reviewed by Alan L. Hayes Margaret Eletta Guider, Daughters of Rahab: Prostitution and the Church of Liberation in Brazil, reviewed by Helen-May Eaton-Ramirez Howard Clark Kee and Irvin Borowski, eds., Removing Anti-Judaism from the Pulpit, reviewed by Dow Marmur Bill McKibben, The Comforting Whirlwind: God, Job, and the Scale of Creation, reviewed by Michael Kolarcik Mercy Amba Oduyoye, Daughters of Anowa: African Women and Patriarchy, reviewed by Diana L. Hayes Marjorie Procter-Smith, Praying with Our Eyes Open: Engendering Feminist Liturgical Prayer, reviewed by Pamela Ann Moeller Ted A. Campbell, Christian Confessions: A Historical Introduction, reviewed by Philip G. Ziegler Anne E. Carr, Transforming Grace: Christian Tradition and Women' s Experience, reviewed by Grace Kim Gary David Comstock, Unrepentant, Self-Affirming, Practicing: Lesbian/Bisexual! Gay People within Organized Religion, reviewed by Donald C. Smith Dawn De Vries, Jesus Christ in the Preaching of Calvin and Schleiermacher, reviewed by lain G. Nicol Willem B. Drees, Religion, Science and Naturalism, reviewed by Donald Wiebe David J. Gouwens, Kierkegaard as Religious Thinker, reviewed by Abrahim H. Khan Colin Grant, A Salvation Audit, reviewed by Nancy L. Cocks Moshe Idel and Bernard McGinn, eds., Mystical Union in Judaism, Christianity and Islam: An Ecumenical Dialogue, reviewed by Dow Marmur Gordon D. Kaufman, God-Mystery-Diversity; Christian Theology in a Pluralistic World, reviewed by DarylCulp Julian Kunnie, Models of Black Theology: Issues in Class, Culture and Gender, reviewed by Ogbu U. Kalu Geiko Miiller-Fahrenholz, God's Spirit: Transforming a World in Crisis, reviewed by Philip G. Ziegler Mark I. Wallace. Fragments, of the Spirit: Nature, Violence, and the Renewal of Creation, reviewed by Philip G. Ziegler Anne E. Patrick, Liberating Conscience: Feminist Explorations in Catholic Moral Theology, reviewed by Bridget Campion Terence Penelhum, Reason and Religious Faith, reviewed by Abrahim H. Khan John Polkinghorne, The Faith of a Physicist, reviewed by Donald Wiebe Jung Suk Rhee, Secularization and Sanctification: A Study of Karl Barth's Doctrine of Sanctification and Its Contextual Application to the Korean Church, reviewed by Carl F. Starkloff John J. Robertson, Jr., The Loss and Recovery of Transcendence: The Will to Power and the Light of Heaven, reviewed by Brian J. Walsh Christoph Schwabel, ed., Trinitarian Theology Today: Essays on Divine Being and Act, reviewed by Myroslaw Tataryn Thomas F. Torrance., The Christian Doctrine of God: One Being, Three Persons, reviewed by Myroslaw Tataryn Harold Wells, A Future for Socialism? Political Theology and the "Triumph of Capitalism", reviewed by Donald C. Smith Stephen N. Williams, Revelation and Reconciliation: A Window on Modernity, reviewed by Greg Robertson Pamela Dickey Young, Christ in a Post-Christian World, reviewed by Cora Twohig-Moengangongo