Effects of urotensin-II on cerebral blood flow and ischemia in anesthetized rats.
Urotensin-II (U-II) is a cyclic peptide identified recently in many mammalian species including man. U-II and its receptor are expressed in the central nervous system, in the cardiovascular system and in other peripheral tissues. Although this peptide has been reported initially to be a potent vasoconstrictor, increasing evidence shows that its vascular actions strongly depend on species and vascular beds. Here we analyzed the effects of U-II administration on cerebral blood flow (CBF) under physiological conditions and following cerebral ischemia in rats. Although intravenous injection of U-II had minimal effects on CBF as measured by the technique of laser Doppler flowmetry, its administration (10 nmol) into the lateral cerebral ventricle induced gradual and long lasting increase in CBF (+61% at 1 h post-injection, p<0.05). These U-II-mediated CBF increases were not related to the transient systemic pressor actions of the peptide and were reduced by nitric oxide synthase inhibition (61 vs 17%, p<0.05). Intracerebroventricular administration of U-II following the induction of cerebral ischemia, failed to alter residual CBF in the affected cerebral hemisphere. Nonetheless, following reperfusion (90 min after ischemia), U-II-treated animals displayed a remarkable hyperperfusion compared to vehicle-treated rats (+168%, p<0.05). The volume of infarction was significantly increased in U-II-treated rats (+40%, p<0.05). These results provide the first evidence that U-II increases cerebral blood flow when administered into the cerebral ventricle and exacerbates brain damage following an ischemic insult.
Chuquet
Julien
J
Université de Caen, CNRS-UMR 6185, Centre Cyceron, Caen, France.
Lecrux
Clotilde
C
Chatenet
David
D
Leprince
Jérôme
J
Chazalviel
Laurent
L
Roussel
Simon
S
MacKenzie
Eric T
ET
Vaudry
Hubert
H
Touzani
Omar
O
D000704:Analysis of Variance; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D007511:Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014579:Urotensins / Q000627:therapeutic use*
D014579:Urotensins; C029677:urotensin II