Age-Related Changes and Effects of Mild Hypothermia on Carotid Artery Reactivity in Newborn Rats

Giacomo Cavallaro, Else Bijker, Eveline Strackx, Johan S. H. Vles, Danilo Gavilanes, Eduardo Villamor*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Therapeutic hypothermia has become a standard neuroprotective treatment in term newborn infants following perinatal asphyxia. Hypothermia-induced changes in the reactivity of the vessels supplying the brain might play a role in its therapeutic or side effects. We investigated the putative age-related changes and the effect of clinically relevant cooling (33 degrees C) on the reactivity of the newborn rat carotid artery. Carotid artery rings from 2-3 days old and 9-10 days old rats were mounted in myographs and studied at 33 degrees C and 37 degrees C. Hypothermia did not significantly affect the contractions induced by KCl and U46619, nor the relaxations induced by acetylcholine (ACh), the nitric oxide (NO) donor sodium nitroprusside (SNP), the NO-independent stimulator of soluble guanylate cyclase (sGC) BAY 41-2272, the beta-adrenoceptor agonist isoproterenol, the adenylate cyclase activator forskolin, and acute hypoxia (PO2 3 kPa). The relaxations induced by ACh, isoproterenol, the beta (2)-adrenoceptor agonist salbutamol, the beta (3)-adrenoceptor agonist CL-316243 and acute hypoxia increased with postnatal age and were impaired by endothelium removal or by inhibition of NO synthase (L-NAME) or sGC (ODQ). In contrast, the relaxations induced by SNP, BAY 41-2272 and forskolin were endothelium-independent and did not change with age. In conclusion, mild hypothermia (33 degrees C) does not affect the reactivity of neonatal rat carotid arteries. Our data suggest a reduced NO bioavailability in the carotid artery during the first days of life. This transient reduction in endothelium-dependent relaxation might play a role in the adaptation of the circulatory system to birth and in the neonatal vascular response to insults such as hypoxia.
Original languageEnglish
Pages (from-to)91-101
JournalCns & Neurological Disorders-Drug Targets
Issue number1
Publication statusPublished - 2015


  • beta-adrenoceptors
  • developmental changes
  • endothelium
  • hypothermia
  • hypoxia
  • nitric oxide


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