Prehypoxic clonidine administration improves vasomotricity of isolated rat aorta during reoxygenation.
OBJECTIVE
Clonidine, an alpha-2 adrenoceptor (A2A) agonist, improves posthypoxic function of several organs in humans and animal models. Mechanisms underlying these effects are not fully understood. A competent vasomotricity during reperfusion participates in the organ's recovery. This study investigates the specific effect of clonidine administration before hypoxia on posthypoxic vasomotricity in a rodent model.


METHODS
Isolated aortic rings from young rats were submitted to hypoxia/reoxygenation (20/40 min). Clonidine (10(-5) mol l(-1)), alone or with various receptor antagonists such as rauwolscine (specific A2A antagonist), ARC239 (A2B/C-prefering A antagonist), BRL44408 (A2AA antagonist), nitrogen oxide synthase inhibitor (Nω-nitro-L-arginine methyl ester) or cyclooxygenase inhibitor (indometacin), was administered in two randomized baths and washed out before hypoxia. Two other baths constituted the control group. In some experiments, clonidine was substituted by UK14.304 (A2A agonist). In all baths, posthypoxic endothelium-dependent dilatation (PED) and posthypoxic contraction were assessed.


RESULTS
Clonidine improves PED (P = 0.002) and posthypoxic contraction (P = 0.001). Rauwolscine (P = 0.803) and ARC239 (P = 0.236) abolished clonidine-induced PED improvement. In the presence of BRL44408, clonidine increases posthypoxic endothelial dysfunction (P = 0.001). UK14.304 (P = 0.954) does not mimic the clonidine effect on PED. Concerning posthypoxic contraction, rauwolscine (P = 0.917), endothelial removal (P = 0.687), ARC239 (P = 0.118) or BRL44408 (P = 0.204) prevents the clonidine effect, but UK14.304 induces it (P = 0.005). Nω-Nitro-L-arginine methyl ester (P = 0.026) does not abolish it. Indometacin prevents it on PED and posthypoxic contraction (P = 0.678 and P = 0.851, respectively).


CONCLUSIONS
Clonidine improves posthypoxic vasomotricity on isolated aortic rings. Concerning PED, two endothelial A2A subtypes are required. The clonidine effect on posthypoxic contraction requires endothelial A2A. Nitrogen oxide does not seem to be involved. Concerning the clonidine effect on PED and posthypoxic contraction, cyclooxygenase metabolites seem to be involved.
Department of Anaesthesiology, Cliniques Universitaires UCL de Mont-Godinne, Université Catholique de Louvain, Yvoir, Belgium. maximilien.gourdin@uclouvain.be
Maximilien J
MJ
Gourdin
Olivia
O
Ponchau
Jacques
J
Jamart
Marc
M
De Kock
D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D015687:Cell Hypoxia; D003000:Clonidine / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000187:drug effects / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
D058647:Adrenergic alpha-2 Receptor Agonists; D043705:Receptor, Adenosine A2A; D011451:Prostaglandin-Endoperoxide Synthases; D003000:Clonidine; D010100:Oxygen