PREVENTION OF CEREBRAL VASOSPASM BY VASODILATORY PEPTIDE MAXADILAN FOLLOWING SUBARACHNOID HEMORRHAGE IN RABBITS

Maxadilan is a vasodilatory peptide isolated from the blood-feeding sa nd fly Lutzomyia longipalpis. Its vasodilatory activity, estimated by the formation of erythema on rabbit skin, is greater than those of cal citonin gene-related peptide, vasoactive intestinal polypeptide and pi tuitary adenylyl cyclase activating polypeptide (PACAP). We have recen tly demonstrated that maxadilan is a specific agonist for the PACAP ty pe I receptor, which is widely distributed in brain. Therefore, we wer e interested in the vasodilatory effect of maxadilan on cerebral arter ies and the possibility of its clinical use for the delayed cerebral v asospasm following subarachnoid hemorrhage (SAH). In the first experim ent, 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 pr olong 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 experi ments were performed to implant the maxadilan tablet (n=7) and the pla cebo tablet (n=6) into the cisterna magna after the induction of exper imental SAH in rabbits. The spastic response of the basilar artery was maximum on day three in the placebo-treated groups. In contrast, we o bserved no significant change in the arterial diameter until day five in the rabbits treated with the maxadilan tablet. These data suggest t hat maxadilan may have therapeutic potency in treating cerebral vasosp asm. (C) 1998 Elsevier Science B.V.