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

Research output: Contribution to journalArticle

Abstract

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°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°C and 37°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 β -adrenoceptor agonist isoproterenol, the adenylate cyclase activator forskolin, and acute hypoxia (PO2 3 kPa). The relaxations induced by ACh, isoproterenol, the β 2-adrenoceptor agonist salbutamol, the β 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°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
Number of pages11
JournalCNS and Neurological Disorders - Drug Targets
Volume14
Issue number1
Publication statusPublished - Jan 1 2015

Keywords

  • Developmental changes
  • Endothelium
  • Hypothermia
  • Hypoxia
  • Nitric oxide
  • β-adrenoceptors

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology
  • Medicine(all)

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