Heart cyclic nucleotide responses to sustained aortic constriction in neonatal and adult rats

The present studies examined adenosine and guanosine 3',5'-cyclic monophosphate (cAMP and cGMP) levels in left ventricular tissue of neonatal and adult rats subjected to 3-10 days of abdominal aortic constriction. Left ventricular cAMP levels were elevated after 3 days of pressure overloading in neonatal rats (2,274 +/- 430 pmol/g; mean +/- SE) compared with composite control values (1,280 +/- 124) obtained from sham-operated neonates, sham-operated adults, and aortic-constricted adult groups. cAMP levels declined progressively until, at 10 days after aortic constriction, values were lower (681 +/- 25 pmol/g) than control (1,621 +/- 107). Left ventricular cGMP level was higher in sham-operated neonatal (38 +/- 3 pmol/g) than in sham-operated adult rats (17 +/- 1) at 3 and 10 days postsurgery, but pressure overloading exerted no effect on cGMP measurements. Adenylate cyclase activity in left ventricular tissue homogenate was higher in 3-day sham-operated neonatal (58 +/- 3 pmol X mg protein-1 X min-1) compared with sham-operated adult (10 +/- 1) rats as the result of augmented nonmuscle cell activity. Elevated cAMP values in 3-day, pressure-overloaded neonates occurred despite lower adenylate cyclase activity (44 +/- 2), via degradative modulation (cAMP phosphodiesterase). Guanylate cyclase activity in left ventricular tissue was consistent with prevailing cGMP levels and was not influenced by aortic constriction. The present experiments show that neonatal cardiac enlargement is associated with biphasic alterations in cAMP level which are modulated, at least in part, via degradative reactions.