Studies on potential involvement of protein kinase C in glomerular insensitivity to atrial natriuretic factor on low sodium intake.
BACKGROUND
Atrial natriuretic factor (ANF)-induced increase in glomerular filtration rate (GFR) is inhibited on low sodium intake. It has been shown that activation of renin-angiotensin system on low sodium intake antagonizes the biological effect of ANF by interfering in the intracellular metabolism of cGMP. We have previously indicated that the renin-angiotensin system increases activity of Ca2+/calmodulin dependent-cyclic GMP phosphodiesterase (cGMP-PDE) in glomeruli and thereby inhibits the ANF-induced increase in GFR in low sodium-treated rats. The aim of the present study was to investigate whether low sodium intake might change glomerular cGMP metabolism by the alternative branch of the signal transduction pathway, namely protein kinase-C (PKC) activation.


METHODS
cGMP formation and PKC activity were examined in isolated glomeruli from the rats maintained for five days on a normal or a low sodium diet. Renal hemodynamic parameters in clearance experiments during infusion of ANF (0.5 Kg/min/kg body weight) in both groups of rats were also evaluated.


RESULTS
Low sodium intake inhibited ANF-dependent increase in GFR and nephrogenous cGMP excretion, whereas urinary sodium excretion did not differ appreciably in rats on either diet. The basal and ANF-stimulated cGMP formation in isolated glomeruli was significantly inhibited in low sodium-treated rats as compared to normal sodium-treated rats. The inhibitory effect of low sodium intake on basal and ANF-stimulated glomerular cGMP formation was completely prevented by a selective cGMP-PDE inhibitor, zaprinast, but not affected by PKC activator, PMA, or PKC inhibitor, H-7. The activity of PKC in glomeruli neither in membrane fraction nor in cytosol fraction did not differ significantly between normal and low sodium-treated rats.


CONCLUSIONS
These results demonstrate that the blunted glomerular response to ANF in rats on low sodium intake is due to decrease ability of cGMP formation in glomeruli by increasing activity of cGMP-PDE without altering activity of PKC.
Kalinowski
L
L
Department of Laboratory Medicine, Medical University of Gdansk and Laboratory of Cellular and Molecular Nephrology, Medical Research Center of the Polish Academy of Science, Poland. lekal@amg.gda.pl
Szczepańska-Konkel
M
M
Jankowski
M
M
Angielski
S
S
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D006152:Cyclic GMP / Q000096:biosynthesis; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D012964:Sodium / Q000008:administration & dosage*
D004791:Enzyme Inhibitors; D009320:Atrial Natriuretic Factor; D012964:Sodium; D011493:Protein Kinase C; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP