Intra-arterial simultaneous administration of anandamide attenuates endothelin-1 induced vasospasm in rabbit basilar arteries.

ABSTRACT

BACKGROUND: Anandamide induces not only endothelium-dependent vasodilatation through cannabinoid receptors but also some endothelium- independent vasodilator effect by calcitonin gene-related peptide release through vanilloid receptors. Endothelin-1, a powerful vasoconstrictive peptide derived from endothelial cells, has been shown to be converted to its active form after cleaving by a vascular matrix metalloproteinase which is also involved in inactivation of calcitonin gene-related peptide. The purpose of this study was to investigate whether anandamide inhibits the acute vascular and morphological effects of Endothelin-1 applied intra-arterially on rabbit basilar arteries. METHOD: Fifteen albino rabbits were anaesthetised and underwent placement of a vertebral artery catheter for angiography of the basilar artery. Animals were divided, arbitrarily, into animals in which there was either intra-arterial injection of saline (Group I, n=5), Endothelin-1 (Group II, n=5) and Endothelin-1 and anandamide (Group III, n=5). The diameter of the basilar artery between the pre and post injection angiograms was measured in each of the three groups and transmission electron microscopic investigations on basilar arteries were performed. FINDINGS: Angiographic studies showed that simultaneous administration of anandamide significantly attenuated Endothelin-1 induced vasoconstriction. Furthermore, it was demonstrated that anandamide reversed the morphological changes induced by Endothelin-1 on the vessel wall. INTERPRETATION: These results indicated that anandamide overcomes the angiographic and morphological effects of intrarterially administered ET-1 induced vasospasm in rabbit basilar arteries probably by induction of CGRP related vasodilatation through vanilloid receptors and prevents the acute ET-1 induced ultrastructural vessel wall damage.