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Am J Perinatol 2021; 38(12): 1320-1329
DOI: 10.1055/s-0040-1712953
Original Article

Effects of Neonatal Caffeine Administration on Vessel Reactivity in Adult Mice

Ajay Pratap Singh
1   Department of Pediatrics, Texas Tech University Health Sciences Center, El Paso, Texas
,
Praveen Chandrasekharan
2   Department of Pediatrics, University at Buffalo, Buffalo, New York
,
Sylvia Gugino
2   Department of Pediatrics, University at Buffalo, Buffalo, New York
,
Sara Berkelhamer
2   Department of Pediatrics, University at Buffalo, Buffalo, New York
,
Huamei Wang
2   Department of Pediatrics, University at Buffalo, Buffalo, New York
,
Lori Nielsen
2   Department of Pediatrics, University at Buffalo, Buffalo, New York
,
Vasantha H. S. Kumar 
2   Department of Pediatrics, University at Buffalo, Buffalo, New York
› Author Affiliations Funding None.
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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

Authors' Contributions

Experiments were designed by V.H.S.K and A.P.S. Body weights, tail-cuff measurements, urine, and fecal collections were performed by A.P.S, H.W., and V.H.S.K. Biochemical analysis was performed by L.N. Vessel reactivity studies were conducted by S.G., P.C, A.P.S., and S.B. Analysis and data interpretation were performed by A.P.S., S.G., P.C., S.B., H.W., L.N., and V.H.S.K. Manuscript was revised critically for intellectual content by A.P.S., S.G., P.C., S.B., H.W., L.N., and V.H.S.K. All authors read and approved the final manuscript.


Note

This study was approved by the Institutional Animal Care and Use Committee of the University at Buffalo, Buffalo, NY (IACUC#PED03065N).


Availability of Data and Materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.




Publication History

Received: 28 November 2019

Accepted: 27 April 2020

Article published online:
02 June 2020

© 2020. Thieme. All rights reserved.

Thieme Medical Publishers
333 Seventh Avenue, New York, NY 10001, USA.

 

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