Nitric oxide-mediated retinal arteriolar and arterial dilatation induced by substance P.
OBJECTIVE
The present study was undertaken to compare vasodilatations caused by substance P in retinal arterioles in vivo and in the extraocular retinal central arteries in vitro, and to analyze the mechanisms of its action.


METHODS
In the in vivo study, changes of the retinal arteriolar diameter were continuously measured using a retinal fundus camera. In the in vitro study, changes in the isometric tension were recorded in helical strips of extraocular retinal arteries with and without the endothelium, exposed to aerated bathing media.


RESULTS
In anesthetized dogs, infusions of substance P into the carotid artery produced a dose-dependent dilatation of the intraocular retinal arteriole; the maximal response was obtained about 15 seconds later. The vasodilator response was significantly attenuated by treatment with NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor, and the inhibition was reversed by L-arginine. On the other hand, vasodilatations caused by nitroglycerin were not influenced by L-NA and L-arginine. In the isolated retinal artery just before entering into the eyeball, the addition of substance P produced a concentration-dependent relaxation 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-arginine but not by D-arginine. Treatment with methylene blue or oxyhemoglobin abolished the relaxation induced by substance P, NO, and nitroglycerin.


CONCLUSIONS
Substance P-induced retinal arteriolar dilatation in vivo appears to be mediated by NO synthesized from L-arginine possibly in the endothelium. The endothelium-dependency would be supported by the findings obtained from isolated retinal arteries.
Kitamura
Y
Y
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
Okamura
T
T
Kani
K
K
Toda
N
N
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005451:Fluorescein Angiography; D007091:Image Processing, Computer-Assisted; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D005996:Nitroglycerin / Q000494:pharmacology; D010781:Photography; D012161:Retinal Artery / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D019335:Nitroarginine; D009569:Nitric Oxide; D013373:Substance P; D001120:Arginine; D005996:Nitroglycerin