Although the role of the second messenger cGMP and its effectors, cGMP-dependent protein kinases (cGKs) is quite well known in other organs, only little information exists regarding the function of these signalling molecules in the kidney. Previous studies have shown that cGKII could be involved in regulation of renin secretion and modulation of diverse channels (e.g. AQP2). It is known that ANP (atrial natriuretic peptide) causes diuresis and natriuresis. Furthermore, renal interstitial cGMP is shown to mediate pressure-natriuresis. However, the downstream effectors of ANP/cGMP remain unclear. Therefore, we investigated if renal parameters in different conditions (basal, salt diets, starving, water load) are dependent on cGKII by using a genetically modified mouse model (cGKII-KO). We could not detect any differences between WT and cGKII-KO during basal or starving conditions, except for a slightly decreased urine output/decreased GFR due to a significantly lowered amount of creatinine in urine during a normal salt diet. Thus, cGKII is proposed to be involved only to a minor extent in regulating the renal concentration ability during different salt loads/starving.

When mice were subjected to a volume expansion (performed by application of an 10mM glucose-solution (3% of BW) via feeding needle), WT mice exhibited a potent diuresis. In contrast, urine volume was decreased significantly in cGKII-KO, while electrolyte excretion was nearly not affected. Since fine regulation of water excretion occurs mainly in the collecting duct via modulation of AQP2-trafficking, our results suggest that membrane insertion of AQP2 is inhibited by cGMP/cGKII.