Calcium and osmotic stimulation in renin release from isolated rat glomeruli

The effects of changes in osmolality and calcium concentration on renin release (RR) from isolated superfused rat glomeruli were studied. The undisturbed RR followed a first order fall with a half-time of about 100 min (n = 45). Changes in the osmolality between 270 and 350 mOsm/kg resulted in dose-dependent changes in the RR rates. Hypoosmotic treatment stimulated the RR transiently, whereas hyperosmotic treatment produced a sustained inhibition. The dose-response relationship was log-linear between 270 and 320 mOsm/kg. A decrease in osmolality of 20 mOsm/kg gave proportional increases in RR irrespectively of the RR rate preceding the stimulus. Removal of calcium stimulated the RR by 10 times (n = 5, p less than 0.001) and a subsequent decrease in osmolality of 20 mOsm/kg stimulated the RR proportionally to that observed in the series containing 2 mM calcium. A decrease in osmolality was able to stimulate RR (n = 5.5, p less than 0.05) even when the calcium concentration in the medium was simultaneously raised from 0 to 2 mM. A hyperosmotic Ringer (+ 300 mOsm/kg), inhibited RR to very low levels. A subsequent removal of external calcium was now unable to stimulate the release (n = 5.5). In a less hyperosmotic Ringer (+ 50 mOsm), the RR was inhibited, but a removal of external calcium now stimulated RR. It is suggested that the osmosensitivity of the RR process reflects a waterflux-driven fusion of secretory granules with the cell membrane, and that calcium affects an intragranular equilibrium between aggregated, osmotically inert granule content and dissolved, osmotically active granule content.