NITRIC OXIDE-MEDIATED RETINAL ARTERIOLAR AND ARTERIAL DILATATION INDUCED BY SUBSTANCE-P

Purpose. The present study was undertaken to compare vasodilatations c aused by substance P in retinal arterioles in vivo and in the extraocu lar retinal central arteries in vitro, and to analyze the mechanisms o f its action. Methods. In the in vivo study, changes of the retinal ar teriolar diameter were continuously measured using a retinal fundus ca mera. In the in vitro study, changes in the isometric tension were rec orded in helical strips of extraocular retinal arteries with and witho ut the endothelium, exposed to aerated bathing media. Results. In anes thetized dogs, infusions of substance P into the carotid artery produc ed a dose-dependent dilatation of the intraocular retinal arteriole; t he maximal response was obtained about 15 seconds later. The vasodilat or response was significantly attenuated by treatment with N(G)-nitro- L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor, and the inh ibition was reversed by L-arginine. On the other hand, vasodilatations caused by nitroglycerin were not influenced by L-NA and L-arginine. I n the isolated retinal artery just before entering into the eyeball, t he addition of substance P produced a concentration-dependent relaxati on only when the endothelium of the strips was intact. Removal of the endothelium abolished the response. The peptide-induced relaxation was abolished by L-NA, whereas relaxations caused by NO and nitroglycerin were unaffected. The inhibitory effect of L-NA was reversed by L-argi nine but not by D-arginine. Treatment with methylene blue or oxyhemogl obin abolished the relaxation induced by substance P, NO, and nitrogly cerin. Conclusion. Substance P-induced retinal arteriolar dilatation i n vivo appears to be mediated by NO synthesized from L-arginine possib ly in the endothelium. The endothelium-dependency would be supported b y the findings obtained from isolated retinal arteries.