Affiliation:
1. 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.
Abstract
We investigated the extent of oxidative stress evoked in the hypertensive rat by measuring plasma levels of 8-epi-prostaglandin F
2α
(8-epi-PGF
2α
), 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-PGF
2α
. 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-PGF
2α
. The norepinephrine-induced increase in 8-epi-PGF
2α
levels could be completely normalized by 3 different classes of antihypertensive drugs: prazosin, an α-adrenergic receptor blocker; hydralazine, a nonspecific vasodilator; and losartan, a specific angiotensin type 1 (AT
1
) 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-PGF
2α
, suggesting that Ang II increases plasma levels of 8-epi-PGF
2α
in both a pressor-independent and an AT
1
receptor–dependent manner. In summary, continuous infusion of both Ang II and norepinephrine potently increases plasma levels of 8-epi-PGF
2α
and thus in vivo oxidative stress. Ang II and norepinephrine seem to induce this increase in 8-epi-PGF
2α
via mechanisms with different pressor dependencies.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Cited by
40 articles.
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