Cardiovascular performance in anesthetized rats pretreated with 1,3-bis(2-chloroethyl)-1-Nitrosourea (BCNU)

Cardiovascular function was studied in anesthetized rats at weekly intervals following their pretreatment with single i.p. doses of BCNU (20 mg/kg). Over the first two weeks post-treatment the predominant effects were on total peripheral resistance. Femoral artery diastolic and mean pressures increased with a corresponding decrease in pulse pressure. Thereafter, apparent cardiac effects were also manifest by decreases in systolic and mean pressures, and possibly heartrate. Diastolic and pulse pressures also declined in this second phase. The water content of caudal artery segments from these rats decreased from 82.3 +/- 0.6% in controls to 78.4 +/- 0.6% (P less than 0.05) at 4 weeks post treatment. The total collagen content of these segments had increased 35% over controls as early as 2 weeks after BCNU while total protein content remained unchanged. Whole body responsiveness to the pressor effects of bolus injections of norepinephrine was significantly diminished only at the 4-week sampling time. The cardiovascular toxicity of BCNU may be a complex of direct effects of the drug on vascular endothelia and secondary effects associated with the cholestasis which develops over a similar time course.