Tocopherol inhibits the relaxing effect of terbutaline in the respiratory and reproductive tracts of the rat: the role of the oxidative stress index.
OBJECTIVE
Reactive oxygen species play a role in the signal transduction of beta-adrenergic receptors. We investigated whether an antioxidant (tocopherol) can reduce the effect of terbutaline in beta-2-adrenergic receptor (β2-AR)-regulated smooth muscles.


METHODS
Contractility of the tissues from nonpregnant (trachea) and 22-day-pregnant (myometrium and cervix) rats was investigated in an isolated organ bath. The tracheal and uterine β2-AR expressions were increased by 17-beta-estradiol valerate (E2) and progesterone (P4), respectively. The accumulation of cyclic-AMP (cAMP), and the total oxidant (TOS) and total antioxidant status (TAS) were also measured. The oxidative stress index (OSI) was defined as the ratio of TOS and TAS.


RESULTS
Terbutaline (10(-10)-10(-5)M) decreased the contractions in the nontreated and the P4-pretreated myometria, but tocopherol (10(-7)M) did not alter these actions. Terbutaline (10(-6)M) increased the cervical resistance both in the nontreated and in the P4-treated samples, while tocopherol reduced this action only in the P4-treated cervices. Terbutaline (10(-9)-10(-4)M) reduced the tracheal tones both in the nontreated and in the E2-treated tissues, while tocopherol reduced these effects. The changes in the intracellular cAMP levels of the tissues were in harmony with the isolated organ results. The OSI was highest in the trachea and lowest in the pregnant myometrium.


CONCLUSIONS
A higher OSI is linked to a higher tocopherol sensitivity of beta-mimetic-induced relaxation. Our results suggest that the antiasthmatic effect of beta-mimetics may worsen, while their tocolytic effect may remain unchanged during parallel tocopherol administration.
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Hungary.
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Hódi
Department of Laboratory Medicine, Faculty of Medicine, University of Szeged, Hungary.
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Földesi
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Hungary.
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Ducza
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Hungary.
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Hajagos-Tóth
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Hungary.
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Seres
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Hungary.
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Klukovits
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Hungary. Electronic address: gaspar@pharm.u-szeged.hu.
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Gáspár
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015153:Blotting, Western; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D055703:Reproductive Physiological Phenomena / Q000187:drug effects*; D012137:Respiratory System / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013726:Terbutaline / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D024505:Tocopherols / Q000494:pharmacology*
D000975:Antioxidants; D016877:Oxidants; D017382:Reactive Oxygen Species; D018343:Receptors, Adrenergic, beta-2; D000242:Cyclic AMP; D013726:Terbutaline; D024505:Tocopherols
Antioxidant; Beta-adrenergic receptor; Cervix; Myometrium; Oxidative stress index; Pregnancy; ROS; Tocopherol; Trachea