Role of eicosanoids in alteration of membrane electrical properties in isolated mesenteric arteries of salt-loaded, Dahl salt-sensitive rats

1 The role of eicosanoids in altered membrane electrical properties of Dahl salt-sensitive (DS) rats was investigated, by use of conventional microelectrodes technique, in isolated superior mesenteric arteries of DS rats and Dahl salt-resistant (DR) rats fed either a high or low salt diet. 2 The membrane was significantly depolarized in salt-loaded DS rats compared with the other three groups. In addition, the arteries of salt-loaded DS rats exhibited spontaneous electrical activity. 3 Spontaneous electrical activity in salt-loaded DS rats was inhibited by the following: indomethacin, a cyclo-oxygenase inhibitor; ONO-3708, a prostaglandin H-2/thromboxane A(2) receptor antagonist; OKY-046, a thromboxane A(2) synthase inhibitor; nicardipine, a Ca2+-channel antagonist and by Ca2+-free solution. In addition, spontaneous electrical activity was enhanced by a thromboxane A(2) analogue and by prostaglandin H-2. Spontaneous electrical activity was unaffected by phentolamine, atropine and tetrodotoxin. 4 Membrane potential in arteries of salt-loaded DS rats was not affected by either indomethacin or ONO-3708. 5 Spontaneous contraction, sensitive to indomethacin, was present, and contractile sensitivity to high potassium solution was enhanced in arteries of salt-loaded DS rats. 6 These findings suggest that eicosanoid action, together with membrane depolarization, may lead to the activation of voltage-dependent Ca2+-channels, thereby causing spontaneous electrical activity in mesenteric arteries of salt-loaded DS rats. In addition, tension data suggest that these changes in membrane properties are related to enhanced contractile activities in salt-loaded DS rats. Mechanisms of depolarization remain to be determined.