AJP - Heart and Circulatory Physiology, Vol 271, Issue 1 159-H165, Copyright © 1996 by American Physiological Society

ARTICLES

Formation of an F2-isoprostane in vascular smooth muscle cells by elevated glucose and growth factors

R. Natarajan, L. Lanting, N. Gonzales and J. Nadler
Department of Diabetes, Endocrinology, and Metabolism, City of Hope Medical Center, Duarte, California 91010, USA.

Recently a series of non-cyclooxygenase-derived prostanoids were identified in vivo in humans and in animal models of free radical injury as products of free radical-catalyzed peroxidation of arachidonic acid. One of these, an F2-isoprostane, 8-epiprostaglandin F2 alpha (8-epi-PGF 2 alpha), is a potent renal vasoconstrictor and can increase vascular smooth muscle cell (VSMC) DNA synthesis. In the present study we have evaluated whether F2-isoprostanes play a role in diabetic vascular dysfunction by studying the formation of 8-epi-PGF2 alpha in porcine VSMC (PVSMC) cultured under hyperglycemic conditions. 8-Epi-PGF2 alpha levels were quantitated by a specific enzyme immunoassay. We also examined whether certain VSMC growth factors, such as angiotensin II, platelet-derived growth factor, and transforming growth factor-beta, could also regulate the formation of 8-epi-PGF2 alpha. We observed that PVSMC cultured under high glucose (HG) conditions produced significantly higher amounts of 8-epi-PGF2 alpha compared with normal glucose (NG) conditions (3.7 +/- 0.13 ng/10(6) cells in HG vs. 2.9 +/- 0.2 ng/10(6) cells in NG, P < 0.05). Furthermore, all three growth factors tested evoked significant dose-dependent formation of 8-epi-PGF2 alpha (ranging from 125 to 220% of control). These results suggest that 8-epi-PGF2 alpha formation, as a result of hyperglycemia or due to growth factor action, may lead to increased VSMC growth and contribute to the complications of diabetes and cardiovascular disease.

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