Title:Age-Related Changes and Effects of Mild Hypothermia on Carotid Artery Reactivity in Newborn Rats
Volume: 14
Issue: 1
Author(s): Giacomo Cavallaro, Else Bijker, Eveline Strackx, Johan S.H. Vles, Danilo Gavilanes and Eduardo Villamor
Affiliation:
Keywords:
β-adrenoceptors, developmental changes, endothelium, hypothermia, hypoxia, nitric oxide.
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.
