SODIUM-NITROPRUSSIDE INCREASES GLOMERULAR CAPILLARY HYDRAULIC CONDUCTIVITY IN ISOLATED RAT GLOMERULI

Sodium nitroprusside (SNP) causes renal vasodilation, increased renal blood flow, and increased renal sodium excretion. Systemic vascular ef fects of SNP are dependent on generation of nitric oxide and increase in smooth muscle intracellular cyclic guanosine monophosphate (cGMP). In the current studies isolated glomeruli were used to determine the e ffects of SNP on glomerular capillary hydraulic conductivity (Lp) and on mesangial tone. The direct effects of the cGMP analogue 8-bromo-cGM P on Lp were studied. Glomeruli were isolated from the superficial ren al cortex of adult male Sprague-Dawley rats weighing 143 to 383 gm. Lp was calculated from videomicroscopic images of individual glomeruli d uring the initial 0.1 second of filtration induced by an albumin oncot ic gradient. Incubation of glomeruli in 10(-3) mol/L SNP increased Lp from a control value of 1.38 +/- 0.08 mu l/min . mm Hg . cm(2) to 1.91 +/- 0.13 mu l/min . mm Hg . cm(2) (p < 0.01). Incubation of glomeruli in 10(-5) mol/L 8-bromo-cGMP increased Lp to a comparable degree from a control value of 2.00 +/- 0.58 mu l/min . mm Hg . cm(2) to 2.39 +/- 0.62 mu l/min . mm Hg . cm(2) (p < 0.03). Increase in Lp was observed independent of any effects on systemic or renal circulations, neural effects, or humoral effects. Changes in mesangial tone were estimated from changes in glomerular volume during 15 minutes of incubation with SNP or control medium. Incubation of glomeruli in 10(-5) mol/L SNP in creased glomerular volume 6%, a consequence of mesangial relaxation. I ncubation of glomeruli in 10(-7) and 10(-3) mol/L SNP did not affect m esangial tone. The results support the hypothesis that SNP acts direct ly on the glomerular permeability barrier rather than by altering mesa ngial tone and capillary filtering surface area. Comparable increase i n Lp with incubation with 8-bromo-cGMP supports the hypothesis that in crease in Lp may be mediated by an increase in cGMP. These findings am consistent with our previous findings that SNP and 8-bromo-cGMP resul t in alterations in the actin cytoskeleton of glomerular epithelial ce lls.