Effect Of Ritodrine On Bilirubin Formation In The Neonatal Rat

Ritodrine hydrochloride (RH) is a β-adrenergic, tocolytic agent. RH activates adenyl cyclase which generates cyclic adenosine monophosphate (cAMP). cAMP is reported to increase hepatic heme oxygenase (HO) activity. Because increased hepatic HO activity has been associated with increased hepatic early-labeled bilirubin (ELB) production, we studied the effect of RH on total bilirubin formation (TBF). Litters of Wistar rats (< 12 hrs old) were divided into groups (3 rats each) of equal weight and given 2 SQ injections of RH (35 mg/kg) or saline at 7 and 5 hrs prior to injection of a radio-labeled hepatic heme precursor, δ-ALA-5-14C (0.6 μCi/12.3 nmol) (t=0). 14CO was collected continuously and was quantitated at t=1, 2, 3, 4, 6, 8, and 12 hrs. The excretion rate of carbon monoxide (VeCO), an index of TBF, was determined at t=0, 2, 4, 6, 8, and 12 hrs. At t=12 hrs, the animals were decapitated and blood and liver were collected. Plasma bilirubin (mg/dl) was measured by a UB Analyzer and HO activity(nmoles bili/min/10 mg prot) was determined spectrophotometrically.