Transient vasodilatory effects of adrenomedullin on cerebral parenchymal microvessels in cats.
We studied the effects of adrenomedullin, structural homology of calcitonin gene-related peptide (CGRP), on the cerebral parenchymal microvessels in cats by our photoelectric method. Adrenomedullin significantly increased cerebral blood volume (CBV) at 0.5 and 1 min after intracarotid injection (0.01-1 nmol/kg, maximum; +0.71 vol% for 0.1 nmol/kg adrenomedullin). Adrenomedullin antagonist, adrenomedullin22-62 (0.01-10 nmol/kg), caused no significant changes in CBV and mean arterial blood pressure. Preinjection of 10 nmol/kg adrenomedullin22-52 blocked the vasodilatory effect of 0.01 nmol/kg adrenomedullin (P < 0.05). Pretreatment of 1 nmol/kg CGRP8-37, which has antagonistic activity against CGRP, also inhibited the vasodilatation of adrenomedullin. The degree of CBV reduction after adrenomedullin22-52 injection was greater than that after CGRP8-37 injection. Adrenomedullin has no major role in the maintenance of resting tone of intracerebral parenchymal vessels. Intravascularly administered adrenomedullin dilates cortical microvessels mainly through the specific adrenomedullin receptor.
Department of Neurology, School of Medicine, Keio University, Tokyo, Japan. takao@mc.med.keio.ac.jp
M
M
Takao
M
M
Tomita
N
N
Tanahashi
M
M
Kobari
Y
Y
Fukuuchi
D053607:Adrenomedullin; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001810:Blood Volume / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D019204:GTP-Binding Proteins / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects; D008833:Microcirculation / Q000187:drug effects; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide; D014665:Vasodilator Agents / Q000494:pharmacology*
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D008565:Membrane Proteins; D010446:Peptide Fragments; D010455:Peptides; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide; D014665:Vasodilator Agents; C104782:adrenomedullin (22-52); C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; D019204:GTP-Binding Proteins; D015740:Calcitonin Gene-Related Peptide