We investigated the extent of oxidative stress evoked in the hypertensive rat by measuring plasma levels of 8-epi-prostaglandin F2&agr;(8-epi-PGF2&agr;), 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&agr;. 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&agr;. The norepinephrine-induced increase in 8-epi-PGF2&agr;levels could be completely normalized by 3 different classes of antihypertensive drugs: prazosin, an &agr;-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&agr;, suggesting that Ang II increases plasma levels of 8-epi-PGF2&agr;in both a pressor-independent and an AT1receptor–dependent manner. In summary, continuous infusion of both Ang II and norepinephrine potently increases plasma levels of 8-epi-PGF2&agr;and thus in vivo oxidative stress. Ang II and norepinephrine seem to induce this increase in 8-epi-PGF2&agr;via mechanisms with different pressor dependencies.