Cyclic nucleotide metabolism was investigated in growing kidneys of rats during compensatory hypertrophy and during neonatal development. After unilateral nephrectomy a mild and short-lasting decrease in cyclic 3':5' adenosine monophosphate (cAMP) was observed in the hypertrophying kidney. In contrast, cyclic 3':5' guanosine monophosphate (cGMP) showed a sharp decline to 20% of control at 15 min and a rapid rise to 200-300% above baseline at 1-72 hr. The alterations in renal tissue levels of cGMP were associated with parallel changes in the soluble, 100,000 X g supernatant guanylate cyclase activity [GTP pyrophosphate-lyase (cyclizing); EC 4.6.1.2]. No change was observed in total cGMP phosphodiesterase (3':5'-cyclic-nucleotide 5'-nucleotidohydrolase; EC 3.1.4.17). In the rapidly growing kidney of newborn rats cAMP levels were 983 i 65 and 833 4 42 pmol/g of kidney at 4 and 7 days after birth, and increased to adult levels (1518 4 57 pmol/g) at 21 days, whereas cGMP levels were 59.8 L 6.8 and 92.5 -13.9 pmol/g at 4 and 7 days and decreased to adult levels (36 I 1.5) at 21 days.The results indicate that compensatory renal hypertrophy and neonatal kidney growth are associated with changes in cAMP and cGMP metabolism. There is evidence for involvement of 3':5'-cAMP and 3':5'-cGMP in the regulation of cellular growth and proliferation in animal cells and bacteria (1-4). In some cells, an increase in cellular cAMP content was shown to be associated with arrest or inhibition of growth, whereas increased cellular cGMP concentrations were associated with cell growth and proliferation (3).One of the models for studying organ growth in vivo is compensatory renal hypertrophy occurring after removal of one kidney (5). It is known that adaptive processes in the hypertrophying kidney occur almost immediately, as evidenced by changes in the metabolism of membrane phospholipids and RNA (6, 7). In the present study we investigated some of the components of the cyclic nucleotide systems in kidneys of rats during the initial phase of renal hypertrophy and during neonatal kidney growth.Marked and rapid changes in cGMP content of hypertrophying kidneys were observed. These changes were accompanied by parallel changes of the soluble guanylate cyclase activity [GTP pyrophosphate-lyase (cyclizing); EC 4.6.1.2]. No change occurred in total cGMP phosphodiesterase activity (3':5'-cyclic-nucleotide 5'-nucleotidohydrolase; EC 3.1.4.17). Cyclic AMP levels showed only a moderate and short-lasting decline. In developing kidneys of newborn rats cAMP increased from 50% of the adult value at 4 days after birth to adult levels at 21 days, whereas cGMP decreased from 200% at 4 days to the adult level at 21 days. Thus, it appears that normal renal growth as well as compensatory renal hypertrophy are associated with changes in cyclic nucleotide metabolism.Abbreviations: cAMP, cyclic 3':5' adenosine monophosphate; cGMP, cyclic 3':5' guanosine monophosphate. 524
MATERIALS AND METHODS
MaterialsAnimals. Adult male Sprague-Dawley rats (200-...