In this study the influence of changes of extracellular osmolarity on renin secretion was characterized using isolated perfused kidneys of rats and mice. Stepwise increases of osmolarity up to 133% of control by addition of NaCl, Na-isethionate, choline-Cl, succinate or glucose led to instantaneous stimulations of renin secretion rates (RSR) up to the 3.5-fold of control, irrespective of the agent used. In contrast, a decrease of osmolarity by lowering the NaCl concentration inhibited RSR. The amplitude of changes of RSR was related to steady state RSR prior to the osmotic challenge. Osmolarity induced changes of RSR were not attenuated by the modulation of NO-formation or EDHF-liberation (pretreatment with L-NAME or acetylcholine) or by the inhibition of prostaglandin synthesis (indomethacin), nor by the blockade of macula densa Na-K-2Cl cotransport function (bumetanide) or of swelling activated chloride channels (DIDS). Moreover, we obtained evidence that the pool of renin secretion excitable by hyperosmolarity is exhaustible and that its complete refilling takes at least two minutes, fitting into the concept about exocytosis proposing the existence of different pools of committed secretory vesicles, which have not yet undergone the final modification for initiation of exocytosis.

These data show, that changes of osmolarity regulate renin release from whole kidneys, an increase stimulating and a decrease inhibiting it and that these effects appear to be of direct nature.