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.
Takao
M
M
Department of Neurology, School of Medicine, Keio University, Tokyo, Japan. takao@mc.med.keio.ac.jp
Tomita
M
M
Tanahashi
N
N
Kobari
M
M
Fukuuchi
Y
Y
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