Angiotensin II and catecholamines increase plasma levels of 8-epi-prostaglandin F(2alpha) with different pressor dependencies in rats.
We investigated the extent of oxidative stress evoked in the hypertensive rat by measuring plasma levels of 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)), 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(2alpha). 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(2alpha). The norepinephrine-induced increase in 8-epi-PGF(2alpha) levels could be completely normalized by 3 different classes of antihypertensive drugs: prazosin, an alpha-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(2alpha), suggesting that Ang II increases plasma levels of 8-epi-PGF(2alpha) 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(2alpha) and thus in vivo oxidative stress. Ang II and norepinephrine seem to induce this increase in 8-epi-PGF(2alpha) via mechanisms with different pressor dependencies.
Aizawa
Toru
T
Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Japan.
Ishizaka
Nobukazu
N
Usui
Shin-Ichi
S
Ohashi
Noriko
N
Ohno
Minoru
M
Nagai
Ryozo
R
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy; D007052:Ibuprofen / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D016861:Cyclooxygenase Inhibitors; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D007052:Ibuprofen; D009638:Norepinephrine