Action of the Na+ ionophore monensin on vascular smooth muscle of guinea-pig aorta.
The effects of the Na+ ionophore monensin on contractile responses were investigated in guinea-pig aorta in normal and high K+ solutions. In normal K+ (5.4 mM) solution, monensin (2 X 10(-5) M) produced a rapid increase in tension followed by slow relaxation. This contraction was markedly inhibited by phentolamine (10(-5) M) or prazosin (10(-6) M) and was accompanied by an increase in tritium efflux from tissue preloaded with [3H]norepinephrine. In the presence of phentolamine, monensin (1-2 X 10(-5) M) or ouabain (1-2 X 10(-5) M) caused only a small and slowly developing contraction. Simultaneous application of these agents caused a more rapid and greater contraction. Either monensin or ouabain gradually increased cellular Na+ and decreased cellular K+ content. When monensin was applied simultaneously with ouabain, there was a rapid increase in cellular Na+ and loss of cellular K+. In high K+ (65.4 mM) solution, monensin (10(-6) M) slightly reduced the increased tension level but when external glucose was omitted monensin markedly inhibited the contraction. A significant decrease in tissue ATP content was observed only when monensin was applied in glucose-free solution. Similarly, hypoxia (N2 bubbling) markedly inhibited the high K+ contraction and decreased the tissue ATP content only in the absence of glucose. These results suggest that monensin produces a neurogenic contraction due to the release of endogenous catecholamines and also produces a myogenic contraction by a decrease in transmembrane Na+ and K+ gradients when the Na+-K+ pump is inhibited by ouabain, and that monensin inhibits aerobic energy metabolism of vascular smooth muscle.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D005663:Furans / Q000494:pharmacology*; D005947:Glucose / Q000502:physiology; D006168:Guinea Pigs; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008985:Monensin / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011224:Prazosin / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D005663:Furans; D010042:Ouabain; D000255:Adenosine Triphosphate; D008985:Monensin; D012964:Sodium; D014700:Verapamil; D005947:Glucose; D011188:Potassium; D009638:Norepinephrine; D011224:Prazosin; D010646:Phentolamine