The effects of ionophores (A23187 and RO2-2985) on renin secretion and renal vasoconstriction

Abstract

The hypothesis that renin release and renal vasoconstriction are both controlled by changes in net ionic flux of calcium has been supported by previous work from this laboratory, and in order to test the concept further the effects of ionophores have been studied. These substances, which are peptides derived from bacterial culture, act by chelating ions and transporting them across cell membranes. Two ionophores, A23187 and RO2-2985, were chosen for their known ability to transport calcium and magnesium. As in the previous experiments, the isolated perfused rat kidney was used and the effects of the ionophores in different concentrations and with different ionic composition of the perfusate were investigated. The results were most clear-cut with A23187 which seems to be more specific in transport of calcium and magnesium. This ionophore in higher concentrations (2 $\times $ 10$^{-6}$ mol l$^{-1}$) caused marked vasoconstriction and inhibition of renin release, whereas at lower concentrations (2 $\times $ 10$^{-7}$ mol l$^{-1}$) there was no vasoconstriction but very marked inhibition of renin release. Both the renal vasoconstriction and the inhibition of renin release were calcium dependent since the effects were abolished by calcium-free perfusate in the presence of the ionophore. In the case of RO2-2985 the results were not so clear-cut but in higher concentrations (2 $\times $ 10$^{-5}$ mol l$^{-1}$) vasoconstriction occurred together with inhibition of renin release. However, unlike A23187, the vasoconstrictor effect was biphasic with an immediate rise, followed by decline, and then a secondary rise. The first component was shown to be dependent on calcium in the perfusion medium, and the second upon magnesium. Inhibition of renin release was most closely related to the presence of calcium in the perfusate but this was not as clear-cut a demonstration as with A23187. As a whole, therefore, the evidence supports the link between renin release, renal vasoconstriction and calcium flux.