Unilateral ureteral obstruction increases glomerular soluble guanylyl cyclase activity.

Journal of the American Society of Nephrology : JASN
K A McDowellL L Norling

Abstract

RBF and GFR are decreased in kidneys after ipsilateral unilateral ureteral obstruction (UUO) for 24 h. Despite net vasoconstriction, vasodilatory mechanisms respond to counterbalance the vasoconstriction: the inhibition of nitric oxide synthase activity is associated with a greater reduction in RBF with ipsilateral UUO. To determine whether the stimulation of soluble guanylyl cyclase differs between glomeruli from obstructed kidneys and normal kidneys, cGMP was measured after stimulation by 10(-3) M sodium nitroprusside (SNP) in glomeruli isolated from the kidneys of Sprague-Dawley rats after 24 h of UUO or sham operation. The generation of intracellular and extracellular (EC) cGMP (femtomoles of cGMP/100 glomeruli/per hour) was measured by RIA. After incubation with SNP, the EC accumulation of cGMP by UUO glomeruli was significantly greater than that by glomeruli from sham-operated rats (P < 0.05). When glomerular studies were repeated in the presence of the phosphodiesterase inhibitor isobutyl methylxanthine, there was no difference in the EC accumulation of cGMP. The direct measurement of cGMP hydrolysis by phosphodiesterase was significantly less in glomerular homogenate from UUO rats compared with sham-operated rats (P < 0...Continue Reading

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