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Prevention of cerebral vasospasm by vasodilatory peptide maxadilan following subarachnoid hemorrhage in rabbits. 1998

T Kaminuma, and H Shimizu, and I Ahmad, and N Ochiai, and R Ehama, and M Ohnuma, and T Banba, and K Watabe, and E A Lerner, and S Imaizumi, and M Tajima, and T Yoshimoto
Shiseido Research Center, Yokohama, Japan.

Maxadilan is a vasodilatory peptide isolated from the blood-feeding sand fly Lutzomyia longipalpis. Its vasodilatory activity, estimated by the formation of erythema on rabbit skin, is greater than those of calcitonin gene-related peptide, vasoactive intestinal polypeptide and pituitary adenylyl cyclase activating polypeptide (PACAP). We have recently demonstrated that maxadilan is a specific agonist for the PACAP type I receptor, which is widely distributed in brain. Therefore, we were interested in the vasodilatory effect of maxadilan on cerebral arteries and the possibility of its clinical use for the delayed cerebral vasospasm following subarachnoid (SAH). In the first experiment, 10(-10) mol/kg of maxadilan (in sterile water) was injected into the cisterna magna three days after the induction of experimental SAH in rabbits (n = 6). Maxadilan dilated spastic basilar arteries within 30 min of the injection, but not at 6 h. In the second experiment, to prolong the vasodilatory effect of maxadilan, tablets containing stearic acid, hydrogenated oil, lactose, hydroxypropylcellulose and 15 mg of maxadilan were prepared. In vitro testing showed that 60% of maxadilan could be released slowly within the initial five days. In vivo experiments were performed to implant the maxadilan tablet (n = 7) and the placebo tablet (n = 6) into the cisterna magna after the induction of experimental SAH in rabbits. The spastic response of the basilar artery was maximum on day three in the placebo-treated groups. In contrast, we observed no significant change in the arterial diameter until day five in the rabbits treated with maxadilan tablet. These data suggest that maxadilan may have therapeutic potency in treating cerebral vasospasm.

UI MeSH Term Description Entries
D008297 Male Males
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D002546 Ischemic Attack, Transient Brief reversible episodes of focal, nonconvulsive ischemic dysfunction of the brain having a duration of less than 24 hours, and usually less than one hour, caused by transient thrombotic or embolic blood vessel occlusion or stenosis. Events may be classified by arterial distribution, temporal pattern, or etiology (e.g., embolic vs. thrombotic). (From Adams et al., Principles of Neurology, 6th ed, pp814-6) Brain Stem Ischemia, Transient,Cerebral Ischemia, Transient,Crescendo Transient Ischemic Attacks,Transient Ischemic Attack,Anterior Circulation Transient Ischemic Attack,Brain Stem Transient Ischemic Attack,Brain TIA,Brainstem Ischemia, Transient,Brainstem Transient Ischemic Attack,Carotid Circulation Transient Ischemic Attack,Posterior Circulation Transient Ischemic Attack,TIA (Transient Ischemic Attack),Transient Ischemic Attack, Anterior Circulation,Transient Ischemic Attack, Brain Stem,Transient Ischemic Attack, Brainstem,Transient Ischemic Attack, Carotid Circulation,Transient Ischemic Attack, Posterior Circulation,Transient Ischemic Attack, Vertebrobasilar Circulation,Transient Ischemic Attacks, Crescendo,Vertebrobasilar Circulation Transient Ischemic Attack,Attack, Transient Ischemic,Attacks, Transient Ischemic,Brainstem Ischemias, Transient,Cerebral Ischemias, Transient,Ischemia, Transient Brainstem,Ischemia, Transient Cerebral,Ischemias, Transient Brainstem,Ischemias, Transient Cerebral,Ischemic Attacks, Transient,TIA, Brain,TIAs (Transient Ischemic Attack),Transient Brainstem Ischemia,Transient Cerebral Ischemia,Transient Cerebral Ischemias,Transient Ischemic Attacks
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013345 Subarachnoid Hemorrhage Bleeding into the intracranial or spinal SUBARACHNOID SPACE, most resulting from INTRACRANIAL ANEURYSM rupture. It can occur after traumatic injuries (SUBARACHNOID HEMORRHAGE, TRAUMATIC). Clinical features include HEADACHE; NAUSEA; VOMITING, nuchal rigidity, variable neurological deficits and reduced mental status. Hemorrhage, Subarachnoid,Perinatal Subarachnoid Hemorrhage,Subarachnoid Hemorrhage, Aneurysmal,Subarachnoid Hemorrhage, Spontaneous,SAH (Subarachnoid Hemorrhage),Subarachnoid Hemorrhage, Intracranial,Aneurysmal Subarachnoid Hemorrhage,Aneurysmal Subarachnoid Hemorrhages,Hemorrhage, Aneurysmal Subarachnoid,Hemorrhage, Intracranial Subarachnoid,Hemorrhage, Perinatal Subarachnoid,Hemorrhage, Spontaneous Subarachnoid,Hemorrhages, Aneurysmal Subarachnoid,Hemorrhages, Intracranial Subarachnoid,Hemorrhages, Perinatal Subarachnoid,Hemorrhages, Spontaneous Subarachnoid,Hemorrhages, Subarachnoid,Intracranial Subarachnoid Hemorrhage,Intracranial Subarachnoid Hemorrhages,Perinatal Subarachnoid Hemorrhages,SAHs (Subarachnoid Hemorrhage),Spontaneous Subarachnoid Hemorrhage,Spontaneous Subarachnoid Hemorrhages,Subarachnoid Hemorrhage, Perinatal,Subarachnoid Hemorrhages,Subarachnoid Hemorrhages, Aneurysmal,Subarachnoid Hemorrhages, Intracranial,Subarachnoid Hemorrhages, Perinatal,Subarachnoid Hemorrhages, Spontaneous
D014665 Vasodilator Agents Drugs used to cause dilation of the blood vessels. Vasoactive Antagonists,Vasodilator,Vasodilator Agent,Vasodilator Drug,Vasorelaxant,Vasodilator Drugs,Vasodilators,Vasorelaxants,Agent, Vasodilator,Agents, Vasodilator,Antagonists, Vasoactive,Drug, Vasodilator,Drugs, Vasodilator
D019476 Insect Proteins Proteins found in any species of insect. Insect Protein,Protein, Insect,Proteins, Insect

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