Studies on potential involvement of protein kinase C in glomerular insensitivityto atrial natriuretic factor on low sodium intake.
Leszek Kalinowski, Mirosława Szczepańska-Konkel, Maciej Jankowski, Stefan Angielski
Med Sci Monit 2001; 7(4): BR628-634
BACKGROUND: Atrial natriuretic factor (ANF)-induced increase in glomerularfiltration rate (GFR) is inhibited on low sodium intake. It has been shown that activation of renin-angiotensinsystem on low sodium intake antagonizes the biological effect of ANF by interfering in the intracellularmetabolism of cGMP. We have previously indicated that the renin-angiotensin system increases activityof Ca2+/calmodulin dependent-cyclic GMP phosphodiesterase (cGMP-PDE) in glomeruli and thereby inhibitsthe ANF-induced increase in GFR in low sodium-treated rats. The aim of the present study was to investigatewhether low sodium intake might change glomerular cGMP metabolism by the alternative branch of the signaltransduction pathway, namely protein kinase-C (PKC) activation.
MATERIAL AND METHODS: cGMP formation andPKC activity were examined in isolated glomeruli from the rats maintained for five days on a normal ora low sodium diet. Renal hemodynamic parameters in clearance experiments during infusion of ANF (0.5Kg/min/kg body weight) in both groups of rats were also evaluated.
RESULTS: Low sodium intake inhibitedANF-dependent increase in GFR and nephrogenous cGMP excretion, whereas urinary sodium excretion did notdiffer appreciably in rats on either diet. The basal and ANF-stimulated cGMP formation in isolated glomeruliwas significantly inhibited in low sodium-treated rats as compared to normal sodium-treated rats. Theinhibitory effect of low sodium intake on basal and ANF-stimulated glomerular cGMP formation was completelyprevented by a selective cGMP-PDE inhibitor, zaprinast, but not affected by PKC activator, PMA, or PKCinhibitor, H-7. The activity of PKC in glomeruli neither in membrane fraction nor in cytosol fractiondid not differ significantly between normal and low sodium-treated rats.
CONCLUSIONS: These results demonstratethat the blunted glomerular response to ANF in rats on low sodium intake is due to decrease ability ofcGMP formation in glomeruli by increasing activity of cGMP-PDE without altering activity of PKC.
Keywords: low sodium intake, atrial natriuretic factor, Glomerular Filtration Rate, cGMP, cGMP-phospodiesterase, Protein Kinase C