title: Age-related changes and effects of mild hypothermia on carotid artery reactivity in newborn rats.
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.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Cavallaro
authors.forename: Else
authors.initials: E
authors.lastname: Bijker
authors.forename: Eveline
authors.initials: E
authors.lastname: Strackx
authors.forename: Johan S H
authors.initials: JS
authors.lastname: Vles
authors.forename: Danilo
authors.initials: D
authors.lastname: Gavilanes
authors.affiliation: Department of Pediatrics, Maastricht University Medical Center (MUMC+), P. Debyelaan 25. P.O. Box 5800. 6202 AZ Maastricht. The Netherlands. e.villamor@mumc.nl.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Villamor
mesh_terms: D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002317:Cardiovascular Agents / Q000494:pharmacology; D002339:Carotid Arteries / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007036:Hypothermia, Induced; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009213:Myography; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature; D013997:Time Factors
chemical_list: D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors