Studies on the mechanism of renin release from isolated superfused rat glomeruli: effects of calcium, calcium ionophore and lanthanum

Abstract

The effects of external medium Ca concentration, the ionophore A23187 and lanthanum on the rate of renin release in vitro were studied with particular emphasis on results obtained from isolated superfused glomeruli of rat kidneys. The response to reduction in superfusate Ca concentration from 2 mM was a graded and reversible increase in the rate of renin release. An increase in release was detectable at 0.2 mM Ca; a 3-fold increase was found 36 min after a change from 2 mM Ca to Ca-free superfusate. A similar relative increase in release resulted from reductions from 0.1 mM to zero Ca, but the absolute amounts of renin released were greater in this latter series. Renin release from kidney cortical slices similarly increased in response to Ca-free incubation medium. The effects of A23187 on renin release were modest. Changing from 2 mM Ca during control periods to Ca-free Ringer with A23187 added caused an attenuated and more delayed increase in release than the change to Ca-free Ringer without ionophore. This difference in response was abolished when glomeruli were superfused with 0.1 mM Ca during the preceding 1 h control period. There was no significant difference in renin release from glomeruli exposed to Ca-free EGTA-Ringer with and without A23187 in the 2 mM Ca series; in the 0.1 mM Ca series the increase in release following a shift to Ca-free EGTA-containing superfusate with A23187 added was significantly greater than in the absence of the ionophore. Addition of lanthanum (1 or 0.05 mM) to Ca-containing as well as Ca-free superfusate resulted in a significant depression of renin release. Subsequent removal of the lanthanum did not restore the rate of release unless EGTA was added; in the latter case a massive increase in renin release occurred resulting in a marked depletion of the remaining renin content of the glomeruli. Ca influences renin release by a direct action on the juxtaglomerular cells. The data support the previous suggestion that basal renin release is a function of active, Ca-dependent cell volume regulation-swelling causing an increase in the release; and further suggest that membrane-bound Ca has a direct effect on the cell membrane permeability to renin. The results exclude the possibility that Ca-stimulated exocytosis is responsible for basal renin release from the juxtaglomerular cells adhering to isolated glomeruli.