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(Hypertension. 2002;39:149.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Angiotensin II and Catecholamines Increase Plasma Levels of 8-Epi-Prostaglandin F₂ With Different Pressor Dependencies in Rats

Toru Aizawa; Nobukazu Ishizaka; Shin-Ichi Usui; Noriko Ohashi; Minoru Ohno; Ryozo Nagai

From the Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine (T.A., N.I., S.-I.U., M.O., R.N.); and the Discovery Research Laboratory, Tanabe Seiyaku Company Limited (N.O.), Tokyo, Japan.

Correspondence to Nobukazu Ishizaka, MD, PhD, Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail nobuishizka-tky{at}umin.ac.jp

We investigated the extent of oxidative stress evoked in the hypertensive rat by measuring plasma levels of 8-epi-prostaglandin F₂ (8-epi-PGF₂), a marker of in vivo oxidative stress. Administration of angiotensin (Ang) II and norepinephrine at doses of 0.7 and 2.8 mg · kg^-1 · d^-1, respectively, resulted in similar significant elevations in plasma levels of 8-epi-PGF₂. A 7-day infusion of Ang II at a nonpressor dose, but not norepinephrine at a nonpressor dose, also increased plasma levels of 8-epi-PGF₂. The norepinephrine-induced increase in 8-epi-PGF₂ levels could be completely normalized by 3 different classes of antihypertensive drugs: prazosin, an -adrenergic receptor blocker; hydralazine, a nonspecific vasodilator; and losartan, a specific angiotensin type 1 (AT₁) receptor antagonist. This finding suggests that the norepinephrine-induced increase is a pressor-dependent event. In contrast, among these antihypertensive drugs, only losartan was effective in inhibiting the Ang II–induced increase in plasma 8-epi-PGF₂, suggesting that Ang II increases plasma levels of 8-epi-PGF₂ in both a pressor-independent and an AT₁ receptor–dependent manner. In summary, continuous infusion of both Ang II and norepinephrine potently increases plasma levels of 8-epi-PGF₂ and thus in vivo oxidative stress. Ang II and norepinephrine seem to induce this increase in 8-epi-PGF₂ via mechanisms with different pressor dependencies.

Key Words: angiotensin II • AT₁ receptor • oxidative stress • isoprostanes • catecholamine

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