Cyclic guanosine monophosphate increases hydraulic conductivity in rabbit and rat CCT

Although guanosine 3',5'-cyclic monophosphate (cGMP) is present in renal nephron segments, there is no information on the role of cGMP as a mediator of renal tubular transport events. We found that an activator of guanylate cyclase (nitroprusside) and 8-bromocGMP (8-BrcGMP) significantly increased hydraulic conductivity in rabbit and rat cortical collecting tubules (CCT) perfused in vitro. The effect of 10(-4) M 8-BrcGMP to increase CCT hydraulic conductivity was reversible and comparable in magnitude and time course to that produced by maximal concentrations of arginine vasopressin. In rabbit CCT, cGMP increased hydraulic conductivity in the presence of phosphodiesterase inhibition with methylisobutylxanthine and in the presence of supramaximal concentrations of arginine vasopressin. Neither nitroprusside nor 8-BrcGMP stimulated adenylate cyclase activity in microdissected CCT. These data demonstrate that cGMP can act independently of either stimulation of adenylate cyclase activity or inhibition of phosphodiesterase activity to increase hydraulic conductivity in the mammalian CCT.