Ca2+-dependent K+ channels are targets for bradykinin B1 receptor ligands and for lipopolysaccharide in the rat aorta

Although rat aorta smooth muscle cells in culture constitutively express bradykinin B1 receptors, the normotensive rat aorta does not respond to the bradykinin B1 receptor agonist des-Arg9-bradykinin, whereas vessels from the spontaneously hypertensive rat (SHR) respond to bradykinin B1 receptor agonists with cell membrane hyperpolarization and relaxation. Bacterial lipopolysaccharide also is inactive on the normotensive rat but hyperpolarizes the SHR aorta. To determine whether this could be due to the increased intracellular Ca2+ concentration ([Ca2+]i) in the SHR, we raised [Ca2+]i in normotensive rats by treatment with thapsigargin. In the thapsigargin-treated aorta, both lipopolysaccharide and des-Arg9-bradykinin induced hyperpolarization, which was reversed by the Ca2+-dependent K+ channel inhibitor iberiotoxin and by the bradykinin B1 receptor antagonists Lys-[Leu8]-des-Arg9-bradykinin and [Leu8]-des-Arg9-bradykinin. Thus the bradykinin B1 receptor, as well as lipopolysaccharide, needs activated Ca2+-dependent K+ channels for functional expression. The two bradykinin B1 receptor inhibitors, however, have effects on Ca2+-dependent K+ channels which are not mediated by bradykinin B1 receptors.