PS-340 Age-related Changes And Effects Of Mild Hypothermia On Carotid Artery Reactivity In Newborn Rats

Introduction 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. Methods Carotid artery rings from 2–3 d-old and 9–10 d-old rats were mounted in myographs and studied at 33 and 37°C. Results 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 (PO 2 3 kPa). The relaxations induced by ACh, isoproterenol, the β 2 -adrenoceptor agonist salbutamol, the β 3 -adrenoceptor agonist CL-316243 and hypoxia increased with postnatal age and were impaired by endothelium removal or by inhibition of NO synthase (L-NAME) or sGC (ODQ). By contrast, the relaxations induced by SNP, BAY 41–2272 and forskolin were endothelium-independent and did not change with age. Conclusions 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.