Cyclic GMP inhibits renin secretion at the level of renal juxtaglomerular cells. This effect is considered to be mediated by the cGMP-dependent protein kinase II. If and how cGK II is involved in the physiological regulation of renin secretion at the organ level and under the in vivo situation is yet unknown.

We have therefore characterized the regulation of renin expression and of renin secretion in mice lacking cGK II. We found that cGK II -/- mice had higher numbers of renin expressing cells under normal conditions, but also during stimulation of the renin system by salt depletion or during inhibition of the renin system by high salt diet. These changes were paralleled by changes of renin mRNA abundance as well as by changes of plasma renin concentration. At the level of the isolated perfused kidney isoproterenol stimulated and angiotensin II inhibited renin secretion in cGK II -/- like in wildtype (wt) mice. Similarly, the pressure dependency of renin secretion was similar in cGK II -/- and in wt animals, at the level of the isolated perfused kidneys.

These findings suggest that cGK II basically is not involved in the basic mechanisms controlling renin secretion at the level of juxtaglomerular cells. Under in vivo settings however, cGK II appears to attenuate renin synthesis and secretion. These findings suggest the existence of factors in vivo that trigger inhibition of the renin system by an action involving cGK II.

Such factors could comprise the family of natriuretic peptides, which stimulate cGMP formation on the one hand and inhibit the renin system on the other.