Abstract
Objective The effects of neonatal caffeine therapy in adults born preterm are uncertain. We
studied the impact of neonatal caffeine on systemic blood pressure, vessel reactivity,
and response to stress in adult mice.
Study Design Mice pups were randomized to caffeine (20 mg/kg/d) or saline by intraperitoneal injection
for 10 days after birth. We performed tail-cuff BP (8/12 weeks), urinary 8-hydroxydeoxyguanosine
and fecal corticosterone (14 weeks), and vessel reactivity in aortic rings (16 weeks)
in adult mice.
Results No differences were noted in systolic, diastolic, and mean blood pressures between
the two groups at 8 and 12 weeks of age. However, norepinephrine-induced vasoconstriction
was substantially higher in aortic rings in CAF-treated male mice. More significant
vasodilator responses to nitric oxide donors in aortic rings in female mice may suggest
gender-specific effects of caffeine. Female mice exposed to caffeine had significantly
lower body weight over-time. Caffeine-treated male mice had substantially higher fecal
corticosterone and urinary 8-hydroxydeoxyguanosine at 14 weeks, suggestive of chronic
stress.
Conclusion We conclude sex-specific vulnerability to the heightened vascular tone of the aorta
in male mice following neonatal caffeine therapy. Altered vessel reactivity and chronic
stress in the presence of other risk factors may predispose to the development of
systemic hypertension in adults born preterm.
Keywords
caffeine - vessel reactivity - blood pressure - stress - newborn - adult mice
