title: Effects of inhibition of neuronal nitric oxide synthase on basal retinal blood flow regulation.
abstract: Nitric oxide (NO) has been observed to regulate blood flow under basal and stimulated conditions in the retina. Recent evidence suggests that NO produced by neuronal nitric oxide synthase (nNOS) may regulate blood flow in addition to that produced by endothelial nitric oxide synthase (eNOS). The objective of the current study was to investigate the contribution of NO produced by nNOS in the regulation of basal retinal blood flow. A non-specific NOS inhibitor N (G)-nitro-l-arginine methyl ester (l-NAME) and the specific nNOS inhibitors 1-(2-trifluoromethylphenyl) imidazole (TRIM) and (4S)-N-(4-amino-5 [aminoethyl] aminopentyl)-N-nitroguanidine (AAAN) were injected into the vitreous (intravitreal) of Long-Evans rats. Vessel diameters, velocities and volumetric blood flow rates (VBF) in the retinal circulation were determined prior to and in 30-min intervals for 4-4.5h after injection. In addition, the basal amount of nNOS in the rat retina was quantified using a specific enzyme linked immunoassay (ELISA). Treatment with l-NAME and TRIM significantly decreased diameters and VBF. Compared with saline, treatment with l-NAME and TRIM produced a significant (p<0.001) decrease of approximately 12-17% in vessel diameters. Treatment with AAAN significantly decreased vessel diameters and venous VBF. Compared with saline AAAN produced a significant decrease of approximately 7% in arterial (p<0.001) and 5% in venous (p=0.011) diameters, respectively. The amount of nNOS in the rat retina was 0.17+/- 0.0147 pmol mg(-1) of dry retina. The results suggest that though inhibition of nNOS decreases basal diameters, constant VBF is maintained in the retinal circulation.
authors: Department of Biomedical Engineering, Illinois Institute of Technology, 3255 South Dearborn Street, Wishnick Hall 314, Chicago, IL 60616 USA.
authors: Shanti R
authors: SR
authors: Tummala
authors: Sanja
authors: S
authors: Benac
authors: Harry
authors: H
authors: Tran
authors: Anand
authors: A
authors: Vankawala
authors: Astrid
authors: A
authors: Zayas-Santiago
authors: Alyssa
authors: A
authors: Appel
authors: Jennifer J
authors: JJ
authors: Kang Derwent
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006146:Guanidines / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007267:Injections; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D009574:Nitro Compounds / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012039:Regional Blood Flow / Q000187:drug effects*; D012171:Retinal Vessels / Q000187:drug effects* / Q000201:enzymology; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D007093:Imidazoles; C508127:N-(4-amino-5-(aminoethyl)aminopentyl)-N'-nitroguanidine; D009574:Nitro Compounds; C098186:1-(2-trifluoromethylphenyl)imidazole; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D019331:NG-Nitroarginine Methyl Ester