Enhancing cGMP in anti-thy1-induced, chronic-progressive glomerulosclerosis: sGC stimulation versus PDEs inhibition

Results Compared to normal controls, sGC mRNA expression (alpha1 sGC +260% and beta1 sGC +310%) and NOstimulated cGMP production (+270%) were up-regulated in the tubulointerstitium of the untreated cGS animals, while its activity was depressed in glomeruli (-50%). As compared to untreated the cGS group, Bay 41-2272 treatment significantly enhanced glomerular and tubulointerstitial NO-cGMP (+92% and +88%) signaling. This went along with markedly reduced glomerular and tubulointerstitial macrophage infiltration (-42% and -50%), number of proliferating cells (-31% and -30%), matrix protein expression (TGF-β protein -36% and -50%) and accumulation (histological matrix score -47% and -42%) as well as improved kidney function (plasma creatinine -57%). In contrast, PTX therapy only moderately, but not significantly affected the above parameters.