Dataset for: LONG-TERM PROGRAMMING EFFECTS ON BLOOD PRESSURE FOLLOWING GESTATIONAL EXPOSURE TO THE IKR BLOCKER DOFETILIDE
2018-03-05T01:49:01Z (GMT) by
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.