Melatonin inhibits the contractile effect of vanadate in the isolated pulmonary arterial rings of rats: possible role of hydrogen peroxide.
The effect and possible mechanism of action of vanadate on the isolated pulmonary arterial rings of normal rats were studied. Pulmonary arterial rings contracted in response to vanadate (0.1-1 mM) in a concentration-dependent manner. Preincubation of the pulmonary arterial rings with 1 mM melatonin significantly reduced the contractile effect of vanadate by more than 60%. Furthermore, addition of hydrogen peroxide (50 microM) or enzymatic generation of hydrogen peroxide by the addition of glucose oxidase (10 U/mL) to the medium containing glucose produced remarkable increases in the pulmonary arterial tension, 46.2 +/- 7.3 and 78.7 +/- 9.7 g tension/g tissue, respectively. Similarly, incubation of the pulmonary arterial rings with 1 mM melatonin significantly reduced the contractile responses of the arterial rings to hydrogen peroxide and glucose/glucose oxidase to 25.7 +/- 2.9 and 24.7 +/- 4.4 g tension/g tissue, respectively. Vanadate, in vitro, significantly stimulated the oxidation of NADH by xanthine oxidase, and the rate of oxidation was increased by increasing either time or vanadate concentration. Similarly, addition of melatonin to a reaction mixture containing xanthine oxidase and vanadate significantly inhibited the rate of NADH oxidation in a concentration-dependent fashion. The results of the present study indicated that vanadate induced contraction in the isolated pulmonary arterial rings, which was significantly reduced by melatonin. Furthermore, the contractile effect of vanadate on the pulmonary arterial rings may be attributed to the intracellular generation of hydrogen peroxide.
Nagi
Mahmoud N
MN
Department of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia. mnagi@ksu.edu.sa
Mansour
Mahmoud A
MA
Al-Shabanah
Othman A
OA
El-Kashef
Hassan A
HA
D000818:Animals; D004347:Drug Interactions; D005947:Glucose / Q000378:metabolism; D005949:Glucose Oxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008550:Melatonin / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014638:Vanadates / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism
D009243:NAD; D014638:Vanadates; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D014969:Xanthine Oxidase; D005947:Glucose; D008550:Melatonin