A slow embryonic heart rate in early-mid gestation is associated with increased risk of
embryonic death and malformation, however the long-term consequences are unknown. We
administered Dofetilide (Dof, 2.5 mg/kg), a drug that produces embryo-specific bradycardia,
to pregnant rats from gestational days 11-14. Embryonic heart rate and rhythm were
determined using embryo culture. Cardiovascular function was assessed in surviving adult
offspring at rest, during acute psychological stress (air jet stress, AJS), and after 7 days of
repeated AJS. Dof reduced embryonic HR by 40% for ~8h on each of the treatment days. On
postnatal day 3, Dof offspring were ~10% smaller. Blood pressure was elevated in adult Dof
rats (systolic blood pressure, night: 103.8±3.9 vs 111.2±3.0 mmHg, P=0.01). While the
pressor response to AJS was similar in both groups (control 17.7±3.4; Dof 18.9±0.9 mmHg,
P=0.74), after 7 days repeated AJS, clear habituation was present in control (P=0.0001) but
not Dof offspring (P=0.48). Only Dof offspring showed a small increase in resting blood
pressure after 7 days repeated stress (+3.9±1.7 mmHg, P=0.05). The results indicate that
embryonic bradycardia programs hypertension and impaired stress adaptation, and have
implications for the maternal use of cardioactive drugs during pregnancy
