UNILATERAL URETERAL OBSTRUCTION INCREASES GLOMERULAR SOLUBLE GUANYLYLCYCLASE ACTIVITY

RBF and GFR are decreased in kidneys after ipsilateral unilateral uret eral obstruction (UUO) for 24 h. Despite net vasoconstriction, vasodil atory mechanisms respond to counterbalance the vasoconstriction: the i nhibition of nitric oxide synthase activity is associated with a great er reduction in RBF with ipsilateral UUO. To determine whether the sti mulation of soluble guanylyl cyclase differs between glomeruli from ob structed kidneys and normal kidneys, cGMP was measured after stimulati on by 10(-3) M sodium nitroprusside (SNP) in glomeruli isolated from t he kidneys of Sprague-Dawley rats after 24 h of UUO or sham operation. The generation of intracellular and extracellular (EC) cGMP (femtomol es of cGMP/100 glomeruli/per hour) was measured by RIA. After incubati on with SNP, the EC accumulation of cGMP by UUO glomeruli was signific antly greater than that by glomeruli from sham-operated rats (P < 0.05 ). When glomerular studies were repeated in the presence of the phosph odiesterase inhibitor isobutyl methylxanthine, there was no difference in the EC accumulation of cGMP, The direct measurement of cGMP hydrol ysis by phosphodiesterase was significantly less in glomerular homogen ate from UUO rats compared with sham-operated rats (P < 0.05). When 10 (-5) M losartan, an angiotensin II receptor inhibitor, was included in glomerular incubations, there was a significant decrease in the EC gl omerular cGMP response to SNP in UUO glomeruli (P < 0.05). This attenu ated response was abolished by the addition of isobutyl methylxanthine . The addition of angiotensin II did not alter the accumulation of cGM P by UUO or sham glomeruli. These studies indicate that decreased phos phodiesterase activity in UUO glomeruli contributes to the enhanced ac cumulation of EC glomerular cGMP after the stimulation of soluble guan ylyl cyclase by SNP. In addition, angiotensin II receptors modulate th is response, suggesting a role for soluble guanylyl cyclase in counter ing angiotensin-mediated vasoconstriction due to UUO.