Evidence for Altered Cyclic Nucleotide Metabolism During Compensatory Renal Hypertrophy and Neonatal Kidney Growth

In adult male Sprague-Dawley rats contralateral nephrectomy was followed by an initial fall of the concentration of cGMP in renal cortical tissue followed by a rise to a peak level of 300 percent of the initial concentration within two hours. cGMP concentration in the remaining renal cortex remained at about 300 percent of the initial value during the subsequent 72 hours and slowly declined to 150-200 percent in the following two weeks. The changes in cGMP concentration were due to exactly parallel changes in the soluble fraction of renal cortical guanylate cyclase activity, while cGMP-phosphodiesterase activity remained unchanged. cAMP concentration after contralateral nephrectomy fell significantly by about 25 percent within two hours and remained below baseline level for up to eight hours. In the kidneys of newborn rats the concentration of cAMP was approximately one-half that found in adult kidneys: it slightly fell between the fourth and the seventh day after birth and subsequently continuously rose to reach adult values approximately two weeks after birth. The concentration of cGMP was significantly greater four days after birth than in adult rats, further rose between the fourth and the seventh day after birth and subsequently gradually declined to adult levels. The increased cGMP concentration appears to be due to an increase of guanylate cyclase activity in total kidney homogenates which, in turn, was mainly due to an increase of the particulate (membrane-bound) fraction of the enzyme. cGMP-phosphodiesterase activity, however, was also increased in respect to adult levels, one or three weeks after birth. Renal growth from the seventh day after birth to adulthood is accompanied by a continuous increase of the ratio cAMP/cGMP. Removal of one kidney four to seven days after birth resulted in a slower increase of this ratio. The data suggest that cGMP may trigger renal growth and that increases of cGMP concentration in the kidneys are the result of a primary increase in the activity of guanylate cyclase.