title: Normalization of aortic function during arousal episodes in the hibernating ground squirrel.
abstract: Hypothermia is commonly used to restrict organ damage during preservation of tissue, but does not offer complete protection. Organ damage after reperfusion/rewarming is amongst others caused by an impairment of vascular properties, particularly endothelium-dependent vasodilatation. We hypothesized that hibernating small animals, which frequently cycle through periods of deep cooling (torpor) and full rewarming (arousal), employ specific mechanisms to preserve vascular function after cooling and reperfusion. Therefore we measured contraction of aortic tissue of hibernating European ground squirrels after 24 h and 7 days of torpor, arousal (1.5 h) and in non-hibernating animals. To assess the role of nitric oxide (NO), experiments were performed in the absence and presence of the NO-synthesis inhibitor, L-NMMA (10(-4) M). Maximum contraction to phenylephrine and angiotensin II was doubled in 7-days torpid animals without a shift in EC50, compared to the other 3 groups. Maximum contraction to KCl was doubled in 7-days torpid animals compared to the arousal group and non-hibernating animals. Relaxation to acetylcholine (ACh) and sodium nitrite in phenylephrine precontracted rings did not differ between groups. In the presence of L-NMMA, the maximum of concentration-response curves for all three vasoconstrictors was increased by about 30% in the arousal group, but unaffected in other groups. L-NMMA completely inhibited ACh-induced relaxation in 24-h torpid animals and non-hibernating animals, but only partially in 7-days torpid animals and in the arousal group. From this we conclude that vascular adaptation proceeds during torpor. Further, increased contractility of aortic tissue during long torpor returns to normal within 1.5 hours of arousal, which is associated with an increased basal NO synthesis. In addition, involvement of NO in agonist-mediated relaxation differs between the various stages of hibernation.Thus, hibernating animals have effectively developed mechanisms to preserve vascular function after cooling and rewarming.
authors.affiliation: Groningen University Institute for Drug Exploration, Department of Clinical Pharmacology, Faculty of Medical Sciences, The Netherlands. R.H.Henning@med.rug.nl
authors.forename: Robert H
authors.initials: RH
authors.lastname: Henning
authors.forename: Leo E
authors.initials: LE
authors.lastname: Deelman
authors.forename: Roelof A
authors.initials: RA
authors.lastname: Hut
authors.forename: Eddy A
authors.initials: EA
authors.lastname: Van der Zee
authors.forename: Hendrik
authors.initials: H
authors.lastname: Buikema
authors.forename: S Adriaan
authors.initials: SA
authors.lastname: Nelemans
authors.forename: Harm
authors.initials: H
authors.lastname: Lip
authors.forename: Dick
authors.initials: D
authors.lastname: De Zeeuw
authors.forename: Serge
authors.initials: S
authors.lastname: Daan
authors.forename: Anne H
authors.initials: AH
authors.lastname: Epema
mesh_terms: D000818:Animals; D001011:Aorta / Q000502:physiology; D001012:Aorta, Abdominal / Q000502:physiology*; D001143:Arousal / Q000502:physiology*; D001158:Arteries / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006605:Hibernation / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D012589:Sciuridae / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III