Modulation by low sodium intake of glomerular response to cicletanine and atrial natriuretic factor

1 The aim of the study was to investigate whether cicletanine (CIC), as a potential inhibitor of cyclic GMP phosphodiesterase, is able to restore glomerular response to atrial natriuretic factor (ANF) in rats under conditions of diet deprived of sodium. We examined the effects of CIC on glomerular filtration rate (GFR), natriuresis and nephrogenous cyclic GMP excretion in response to ANF and the effects of both agents on intracapillary volume and cyclic GMP accumulation in isolated glomeruli of rats on normal and low sodium diets. 2 CIC (0.25 mg min(-1) kg(-1) BW) of ANF (0.5 mu g min(-1) BW) alone, given in pharmacological doses, increased C-in significantly in normal sodium rats, whereas the effect of each agent was blunted in low sodium diet rats. Pretreatment with CIC restored the increase in C-in in response to ANF infusion in low sodium diet rats. In rats on either diet, there were no differences in the extent of diuresis and natriuresis induced by CIC or ANF alone. In contrast to FENa, combined effects of both agents on V and U-Na V in rats on normal and low sodium diets were observed. 3 In normal sodium diet rats, CIC 10(-4) M or ANF 10(-6) M alone inhibited angiotensin II 10(-6) M (AII)-induced decrease in intracapillary volume reflected by the glomerular [H-3]-inulin space (GIS). In contrast, CIC or ANF alone did not inhibit AII-induced decrease in GIS in low sodium diet rats. Both agents given together inhibited AII-induced decrease in GIS in low sodium diet rats. 4 CIC both alone and in combination with ANF increased nephrogenous cyclic GMP excretion and cyclic GMP accumulation in isolated glomeruli of rats on normal and low sodium diets. In rats on either diet, CIC abolished the difference in ANF-stimulated increase in nephrogenous cyclic GMP excretion and cyclic GMP accumulation in glomeruli. 5 These results suggest that CIC and ANF alone induce relaxation of glomeruli and a resultant increase in glomerular filtration rate in normal sodium diet rats; in contrast, these effects are blunted in the low sodium diet rats. CIC restores glomerular response to ANF in low sodium diet rats, apparently involving inhibition of the cyclic GMP phosphodiesterase.