title: Intravenous infusion of adrenomedullin and increase in regional cerebral blood flow and prevention of ischemic brain injury after middle cerebral artery occlusion in rats.
abstract: The intravenous infusion of rat adrenomedullin, at concentrations ranging from 0.1 to 1.0 microgram/kg/min, for 60 min increased the regional cerebral blood flow (rCBF) in a dose-dependent manner in rats. rCBF was measured using a laser Doppler flowmetry device placed on the surface of the parietal cortex. The increase in rCBF induced by 1.0 microgram/kg/min of adrenomedullin was up to 145 +/- 10.8% of controls at 60 min (n = 5, p < 0.001). These concentrations of adrenomedullin did not affect systemic blood pressure or other physiologic parameters, including pH, PaCO2, PaO2, hemoglobin, and blood glucose. Repeated infusion of 1.0 microgram/kg/min of adrenomedullin at 2-h intervals caused tachyphylaxis (n = 5, p < 0.01). Rat adrenomedullin (1.0 microgram/kg/min) demonstrated a more potent effect than the same dose of human adrenomedullin. The C-terminal fragment of human adrenomedullin (0.5 and 5.0 micrograms/kg/min), adrenomedullin22-52, which did not affect rCBF alone, inhibited the effect of rat adrenomedullin (0.5 microgram/kg/min) as a receptor antagonist in a dose-dependent manner. In a model of middle cerebral artery (MCA) occlusion in spontaneously hypertensive rats, pre- and postinfusion of 1.0 microgram/kg/min of adrenomedullin suppressed the reduction in rCBF following MCA occlusion (control, 29 +/- 15.1%; adrenomedullin group, 45 +/- 14.4%; not significant) and decreased the volume of ischemic brain injury (control, 288 +/- 35 mm3; adrenomedullin group, 232 +/- 35 mm3; p < 0.05). These results suggest that adrenomedullin increases rCBF and prevents ischemic brain injury, partly by increasing the collateral circulation.
authors.affiliation: Department of Neurosurgery, Nagoya University School of Medicine, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Dogan
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: N
authors.initials: N
authors.lastname: Koketsu
authors.forename: K
authors.initials: K
authors.lastname: Osuka
authors.forename: K
authors.initials: K
authors.lastname: Saito
authors.forename: M
authors.initials: M
authors.lastname: Takayasu
authors.forename: M
authors.initials: M
authors.lastname: Shibuya
authors.forename: J
authors.initials: J
authors.lastname: Yoshida
mesh_terms: D053607:Adrenomedullin; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications*; D002545:Brain Ischemia / Q000517:prevention & control*; D002536:Cerebral Arteries; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010455:Peptides / Q000008:administration & dosage*; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D010455:Peptides; D014665:Vasodilator Agents; D053607:Adrenomedullin