Altered cerebrovascular regulation in low birthweight swine

• Published in: Comparative biochemistry and physiology. Part A, Molecular & integrative physiology Molecular & integrative physiology, 2022-05, Vol.267, p.111163-111163, Article 111163
• Main Authors: Morton, Jude S., Patton, Breanna, Morse, Cameron J., El Karsh, Zeyad, Rodrigues, Lucas A., Mousseau, Darrell D., Ferguson, David P., Columbus, Daniel A., Weber, Lynn P., Olver, T. Dylan
• Format: Article
• Language: English
• Subjects: Animals; Arteries; Birth Weight; Brain; Brain sparing; Cerebrovascular; Female; Low birthweight; Nitroprusside; Swine; Vasodilation
• ISSN: 1095-6433; 1531-4332
• DOI: 10.1016/j.cbpa.2022.111163

Full-term low birthweight (LBW) offspring exhibit peripheral vascular dysfunction in the postnatal period; however, whether such impairments extend to the cerebrovasculature remains to be elucidated. We used a swine model to test the hypothesis that LBW offspring would exhibit cerebrovascular dysfunction at later stages of life. Offspring from 14 sows were identified as normal birthweight (NBW) or LBW and were assessed at 28 (similar to end of infancy) and 56 (similar to childhood) days of age. LBW swine had lower absolute brain mass, but demonstrated evidence of brain sparing (increased brain mass scaled to body mass) at 56 days of age. The cerebral pulsatility index, based on transcranial Doppler, was increased in LBW swine. Moreover, arterial myography of isolated cerebral arteries revealed impaired vasoreactivity to bradykinin and reduced contribution of nitric oxide (NO) to vasorelaxation in the LBW swine. Immunoblotting demonstrated a lower ratio of phosphorylated-to-total endothelial NO synthase in LBW offspring. This impairment in NO signaling was greater at 28 vs. 56 days of age. Vasomotor responses to sodium nitroprusside (NO-donor) were unaltered, while Leu31, Pro34 neuropeptide Y-induced vasoconstriction was enhanced in LBW swine. Increases in total Y1 receptor protein content in the LBW group were not significant. In summary, LBW offspring displayed signs of cerebrovascular dysfunction at 28 and 56 days of age, evidenced by altered cerebral hemodynamics (reflective of increased impedance) coupled with endothelial dysfunction and altered vasomotor control. Overall, the data reveal that normal variance in birthweight of full-term offspring can influence cerebrovascular function later in life. •Using a swine model, this study investigated whether uncomplicated and full-term low birthweight offspring exhibited altered cerebrovascular regulation in the postnatal period.•Low birthweight offspring displayed evidence of cerebrovascular dysfunction at 28 and 56 days of age.•Low birthweight offspring exhibited elevated cerebral pulsatility index coupled with endothelial dysfunction and altered peptidergic-mediated vasomotor control.•This study highlights that normal variance in birthweight of full-term offspring influences cerebrovascular function at later stages in life.•These findings provide mechanistic insight into epidemiological observations indicating that birthweight affects brain health during childhood as well as increases the severity of cere