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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
› Institutsangaben 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.




Publikationsverlauf

Eingereicht: 28. November 2019

Angenommen: 27. April 2020

Artikel online veröffentlicht:
02. Juni 2020

© 2020. Thieme. All rights reserved.

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

 

  • References

  • 1 Schmidt B, Roberts RS, Davis P. et al; Caffeine for Apnea of Prematurity Trial Group. Caffeine therapy for apnea of prematurity. N Engl J Med 2006; 354 (20) 2112-2121
    CrossrefPubMedGoogle Scholar
  • 2 Schmidt B, Roberts RS, Davis P. et al; Caffeine for Apnea of Prematurity Trial Group. Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med 2007; 357 (19) 1893-1902
    CrossrefPubMedGoogle Scholar
  • 3 Mürner-Lavanchy IM, Doyle LW, Schmidt B. et al; Caffeine for Apnea of Prematurity (CAP) Trial Group. Neurobehavioral outcomes 11 years after neonatal Caffeine therapy for apnea of prematurity. Pediatrics 2018; 141 (05) e20174047
    CrossrefPubMedGoogle Scholar
  • 4 Schmidt B, Roberts RS, Anderson PJ. et al; Caffeine for Apnea of Prematurity (CAP) Trial Group. Academic performance, motor function, and behavior 11 years after neonatal Caffeine citrate therapy for apnea of prematurity: an 11-year follow-up of the CAP randomized clinical trial. JAMA Pediatr 2017; 171 (06) 564-572
    CrossrefPubMedGoogle Scholar
  • 5 Doyle LW, Ranganathan S, Cheong JLY. Neonatal Caffeine treatment and respiratory function at 11 years in children under 1,251 g at birth. Am J Respir Crit Care Med 2017; 196 (10) 1318-1324
    CrossrefPubMedGoogle Scholar
  • 6 Arnaud MJ. The pharmacology of caffeine. Prog Drug Res 1987; 31: 273-313
    PubMedGoogle Scholar
  • 7 Rath P, Nardiello C, Surate Solaligue DE. et al. Caffeine administration modulates TGF-β signaling but does not attenuate blunted alveolarization in a hyperoxia-based mouse model of bronchopulmonary dysplasia. Pediatr Res 2017; 81 (05) 795-805
    CrossrefPubMedGoogle Scholar
  • 8 Teng RJ, Jing X, Michalkiewicz T, Afolayan AJ, Wu TJ, Konduri GG. Attenuation of endoplasmic reticulum stress by caffeine ameliorates hyperoxia-induced lung injury. Am J Physiol Lung Cell Mol Physiol 2017; 312 (05) L586-L598
    CrossrefPubMedGoogle Scholar
  • 9 Dumpa V, Nielsen L, Wang H, Kumar VHS. Caffeine is associated with improved alveolarization and angiogenesis in male mice following hyperoxia induced lung injury. BMC Pulm Med 2019; 19 (01) 138
    CrossrefPubMedGoogle Scholar
  • 10 Nagatomo T, Jiménez J, Richter J. et al. Caffeine prevents hyperoxia-induced functional and structural lung damage in preterm rabbits. Neonatology 2016; 109 (04) 274-281
    CrossrefPubMedGoogle Scholar
  • 11 Aranda JV, Chemtob S, Laudignon N, Sasyniuk BI. Pharmacologic effects of theophylline in the newborn. J Allergy Clin Immunol 1986; 78 (4 Pt 2): 773-780
    CrossrefPubMedGoogle Scholar
  • 12 Hartley TR, Sung BH, Pincomb GA, Whitsett TL, Wilson MF, Lovallo WR. Hypertension risk status and effect of caffeine on blood pressure. Hypertension 2000; 36 (01) 137-141
    CrossrefPubMedGoogle Scholar
  • 13 Mesas AE, Leon-Muñoz LM, Rodriguez-Artalejo F, Lopez-Garcia E. The effect of coffee on blood pressure and cardiovascular disease in hypertensive individuals: a systematic review and meta-analysis. Am J Clin Nutr 2011; 94 (04) 1113-1126
    CrossrefPubMedGoogle Scholar
  • 14 Walther FJ, Erickson R, Sims ME. Cardiovascular effects of caffeine therapy in preterm infants. Am J Dis Child 1990; 144 (10) 1164-1166
    PubMedGoogle Scholar
  • 15 Ulanovsky I, Haleluya NS, Blazer S, Weissman A. The effects of caffeine on heart rate variability in newborns with apnea of prematurity. J Perinatol 2014; 34 (08) 620-623
    CrossrefPubMedGoogle Scholar
  • 16 de Jong F, Monuteaux MC, van Elburg RM, Gillman MW, Belfort MB. Systematic review and meta-analysis of preterm birth and later systolic blood pressure. Hypertension 2012; 59 (02) 226-234
    CrossrefPubMedGoogle Scholar
  • 17 Temple JL. Caffeine use in children: what we know, what we have left to learn, and why we should worry. Neurosci Biobehav Rev 2009; 33 (06) 793-806
    CrossrefPubMedGoogle Scholar
  • 18 Xu D, Zhang B, Liang G. et al. Caffeine-induced activated glucocorticoid metabolism in the hippocampus causes hypothalamic-pituitary-adrenal axis inhibition in fetal rats. PLoS One 2012; 7 (09) e44497
    CrossrefPubMedGoogle Scholar
  • 19 Jobe AH. Caffeine: a lung drug for all very low birth weight preterm infants?. Am J Respir Crit Care Med 2017; 196 (10) 1241-1243
    CrossrefPubMedGoogle Scholar
  • 20 Vázquez-Palacios G, Retana-Márquez S, Bonilla-Jaime H, Velázquez-Moctezuma J. Further definition of the effect of corticosterone on the sleep-wake pattern in the male rat. Pharmacol Biochem Behav 2001; 70 (2-3): 305-310
    CrossrefPubMedGoogle Scholar
  • 21 Lakshminrusimha S, Porta NF, Farrow KN. et al. Milrinone enhances relaxation to prostacyclin and iloprost in pulmonary arteries isolated from lambs with persistent pulmonary hypertension of the newborn. Pediatr Crit Care Med 2009; 10 (01) 106-112
    CrossrefPubMedGoogle Scholar
  • 22 Raju TNK, Buist AS, Blaisdell CJ, Moxey-Mims M, Saigal S. Adults born preterm: a review of general health and system-specific outcomes. Acta Paediatr 2017; 106 (09) 1409-1437
    CrossrefPubMedGoogle Scholar
  • 23 Mattson DL. Comparison of arterial blood pressure in different strains of mice. Am J Hypertens 2001; 14 (5 Pt 1): 405-408
    CrossrefPubMedGoogle Scholar
  • 24 Wilde E, Aubdool AA, Thakore P. et al. Tail-cuff technique and its influence on central blood pressure in the mouse. J Am Heart Assoc 2017; 6 (06) e005204
    CrossrefPubMedGoogle Scholar
  • 25 Lin HY, Lee YT, Chan YW, Tse G. Animal models for the study of primary and secondary hypertension in humans. Biomed Rep 2016; 5 (06) 653-659
    CrossrefPubMedGoogle Scholar
  • 26 Schwertz DW, Penckofer S. Sex differences and the effects of sex hormones on hemostasis and vascular reactivity. Heart Lung 2001; 30 (06) 401-426 , quiz 427–428
    CrossrefPubMedGoogle Scholar
  • 27 Node K, Kitakaze M, Kosaka H, Minamino T, Funaya H, Hori M. Amelioration of ischemia- and reperfusion-induced myocardial injury by 17beta-estradiol: role of nitric oxide and calcium-activated potassium channels. Circulation 1997; 96 (06) 1953-1963
    CrossrefPubMedGoogle Scholar
  • 28 Leloup A, De Moudt S, Van Hove C, Fransen P. Cyclic stretch alters vascular reactivity of mouse aortic segments. Front Physiol 2017; 8: 858
    CrossrefPubMedGoogle Scholar
  • 29 Hayward CS, Kelly RP, Collins P. The roles of gender, the menopause and hormone replacement on cardiovascular function. Cardiovasc Res 2000; 46 (01) 28-49
    CrossrefPubMedGoogle Scholar
  • 30 London GM, Guerin AP, Pannier B, Marchais SJ, Stimpel M. Influence of sex on arterial hemodynamics and blood pressure. Role of body height. Hypertension 1995; 26 (03) 514-519
    CrossrefPubMedGoogle Scholar
  • 31 Sandberg K, Ji H. Sex differences in primary hypertension. Biol Sex Differ 2012; 3 (01) 7
    CrossrefPubMedGoogle Scholar
  • 32 Xue B, Pamidimukkala J, Hay M. Sex differences in the development of angiotensin II-induced hypertension in conscious mice. Am J Physiol Heart Circ Physiol 2005; 288 (05) H2177-H2184
    CrossrefPubMedGoogle Scholar
  • 33 Minamino T, Kitakaze M, Node K, Funaya H, Hori M. Inhibition of nitric oxide synthesis increases adenosine production via an extracellular pathway through activation of protein kinase C. Circulation 1997; 96 (05) 1586-1592
    CrossrefPubMedGoogle Scholar
  • 34 Linden J. Adenosine in tissue protection and tissue regeneration. Mol Pharmacol 2005; 67 (05) 1385-1387
    CrossrefPubMedGoogle Scholar
  • 35 Carroll MA, Doumad AB, Li J, Cheng MK, Falck JR, McGiff JC. Adenosine2A receptor vasodilation of rat preglomerular microvessels is mediated by EETs that activate the cAMP/PKA pathway. Am J Physiol Renal Physiol 2006; 291 (01) F155-F161
    CrossrefPubMedGoogle Scholar
  • 36 Hansen PB, Castrop H, Briggs J, Schnermann J. Adenosine induces vasoconstriction through Gi-dependent activation of phospholipase C in isolated perfused afferent arterioles of mice. J Am Soc Nephrol 2003; 14 (10) 2457-2465
    CrossrefPubMedGoogle Scholar
  • 37 McIntosh VJ, Chandrasekera PC, Lasley RD. Sex differences and the effects of ovariectomy on the β-adrenergic contractile response. Am J Physiol Heart Circ Physiol 2011; 301 (03) H1127-H1134
    CrossrefPubMedGoogle Scholar
  • 38 Yang S, Zhang L. Glucocorticoids and vascular reactivity. Curr Vasc Pharmacol 2004; 2 (01) 1-12
    CrossrefPubMedGoogle Scholar
  • 39 Touma C, Palme R, Sachser N. Analyzing corticosterone metabolites in fecal samples of mice: a noninvasive technique to monitor stress hormones. Horm Behav 2004; 45 (01) 10-22
    CrossrefPubMedGoogle Scholar
  • 40 Ullian ME. The role of corticosteriods in the regulation of vascular tone. Cardiovasc Res 1999; 41 (01) 55-64
    CrossrefPubMedGoogle Scholar
  • 41 Gray K, Bennett M. Role of DNA damage in atherosclerosis--bystander or participant?. Biochem Pharmacol 2011; 82 (07) 693-700
    CrossrefPubMedGoogle Scholar
  • 42 Noren Hooten N, Ejiogu N, Zonderman AB, Evans MK. Association of oxidative DNA damage and C-reactive protein in women at risk for cardiovascular disease. Arterioscler Thromb Vasc Biol 2012; 32 (11) 2776-2784
    CrossrefPubMedGoogle Scholar
  • 43 Vasdev S, Gill VD, Singal PK. Modulation of oxidative stress-induced changes in hypertension and atherosclerosis by antioxidants. Exp Clin Cardiol 2006; 11 (03) 206-216
    PubMedGoogle Scholar
  • 44 Baradaran A, Nasri H, Rafieian-Kopaei M. Oxidative stress and hypertension: Possibility of hypertension therapy with antioxidants. J Res Med Sci 2014; 19 (04) 358-367
    PubMedGoogle Scholar
  • 45 Forlenza MJ, Latimer JJ, Baum A. The effects of stress on DNA repair capacity. Psychol Health 2000; 15 (06) 881-891
    CrossrefPubMedGoogle Scholar
  • 46 Papadopoulou E, Botton J, Brantsæter AL. et al. Maternal caffeine intake during pregnancy and childhood growth and overweight: results from a large Norwegian prospective observational cohort study. BMJ Open 2018; 8 (03) e018895
    CrossrefPubMedGoogle Scholar
  • 47 Bracco D, Ferrarra JM, Arnaud MJ, Jéquier E, Schutz Y. Effects of caffeine on energy metabolism, heart rate, and methylxanthine metabolism in lean and obese women. Am J Physiol 1995; 269 (4 Pt 1): E671-E678
    PubMedGoogle Scholar
  • 48 Kobayashi-Hattori K, Mogi A, Matsumoto Y, Takita T. Effect of caffeine on the body fat and lipid metabolism of rats fed on a high-fat diet. Biosci Biotechnol Biochem 2005; 69 (11) 2219-2223
    CrossrefPubMedGoogle Scholar
  • 49 Velickovic K, Wayne D, Leija HAL. et al. Caffeine exposure induces browning features in adipose tissue in vitro and in vivo. Sci Rep 2019; 9 (01) 9104
    CrossrefPubMedGoogle Scholar
  • 50 Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J 2008; 22 (03) 659-661
    CrossrefPubMedGoogle Scholar
  • 51 Dutta S, Sengupta P. Men and mice: relating their ages. Life Sci 2016; 152: 244-248
    CrossrefPubMedGoogle Scholar
  • 52 Dayanim S, Lopez B, Maisonet TM, Grewal S, Londhe VA. Caffeine induces alveolar apoptosis in the hyperoxia-exposed developing mouse lung. Pediatr Res 2014; 75 (03) 395-402
    CrossrefPubMedGoogle Scholar
  • 53 Jing X, Huang YW, Jarzembowski J, Shi Y, Konduri GG, Teng RJ. Caffeine ameliorates hyperoxia-induced lung injury by protecting GCH1 function in neonatal rat pups. Pediatr Res 2017; 82 (03) 483-489
    CrossrefPubMedGoogle Scholar