Two TYPES OF RELAXATION RESPONSES MEDIATED BY CYCLIC GMP IN CEREBRAL ARTERIES Kenji Kanamaru 1 , Shiro Waga 1 , Tadashi Kojima 1 , Kiyoshige Fujimoto 1 1Department of Neurosurgery, Mie University School of Medicine pp.559-565
Published Date 1989/6/1
DOI https://doi.org/10.11477/mf.1406206328
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It has been reported that endothelium-derived relaxing factor (EDRF) possesses chemical and pharmacological properties that are indistinguish-able from those of nitric oxide (NO). Moreover, NO is the active chemical species responsible for endothelium-independent vasodilation produced by nitrogen oxide-containing substances including gly-ceryl trinitrate (GTN). Both EDRF and GTN ac-tivate soluble guanylate cyclase and consequently increase cyclic GMP level in various artery prepa-rations. However, there have been few reports regarding cyclic GMP accumulation induced by EDRF or GTN in canine cerebral arteries.

Therefore, it was investigated whether EDRF and GTN cause vasodilation through the common pathway mediated by cyclic GMP in the canine basilar artery. The relaxation responses induced by EDRF or GTN were studied in the canine basilar artery by an isometric tension-recording method.EDRF was induced by calcium ionophore A 23187. A 23187 did not relax the vascular tissue in the absence of the endothelial cells. On the other hand, GTN did induce relaxation in either the pre-sence or absence of endothelial cells. FeSO4 at 3x 10-5 M reversed A23187-induced relaxation, but not GTN-induced relaxation (N=10). Since Fe2+ is able to catalyse the formation of O2- in oxyge-nated phosphate buffer, these findings suggest that Fe2+ antagonizes EDRF by inactivating it via the generation of O2-. By the addition of 10-5 M me-thylene blue, both A 23187- and GTN-induced re-laxations were reversed (N=8). Moreover, pretreat-ment with 10-5 M methylene blue augmented contractile responses to 3 x 10-6 M prostaglandin F2a (N=5).

The cyclic GMP content in canine basilar rings was determined by a sensitive radioimmunoassay procedure. Both A 23187 and GTN elicited an in-crease in arterial cyclic GMP accumulation whichcorrelated well with the development of relaxa-tion. Methylene blue at a concentration of 10-5 M antagonized cyclic GMP accumulation in response to A 23187 and GTN. The inhibitory effect of methylene blue may be due to blockade of guany-late cyclase, as the rise in cyclic GMP contents, which accompanied the relaxation induced by ei-ther of the above agents, was abolished.

The relaxation efficacy of GTN occurred in the order of the human basilar artery>canine jugular vein> canine basilar artery. On the other hand, the relaxation efficacy of A 23187 was not signifi-cantly different among these vessels.

These results suggest that GTN may be a more stable and direct relaxant of the cerebral vascular smooth muscle than EDRF, and that, GTN may be potentially effective in the regulation of cerebral blood flow, especially in the human cerebral artery.

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