Our study aimed to characterize the essential cellular pathways along which
nitric oxide (NO) exerts its well-known vasodilatatory properties in the k
idney. Using the isolated perfused rat kidney model we examined the roles o
f potassium channels, cGMP-protein kinase activity and cAMP-phosphodiestera
ses (PDE) in the effect of NO on renovascular resistance. We found that nei
ther potassium channel activity nor G-kinase activity was essential for the
vasodilatatory effect of NO. The effect of NO, however, was essentially mi
micked by pharmacological inhibition of PDE-3, which is a cGMP-inhibitable
PDE. As PDE-3 is strongly expressed in renal preglomerular vessels and NO s
timulates cGMP formation in renal vessels, it appears likely that inhibitio
n of cAMP degradation and consequently the cAMP pathway are crucially invol
ved in mediating the effects of NO on renal vascular resistance.