Effects of inhibition of neuronal nitric oxide synthase on basal retinal blood flow regulation
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 obj...
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| Veröffentlicht in: | Experimental eye research 2009-11, Vol.89 (5), p.801-809 |
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| description | 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 |
| doi_str_mv | 10.1016/j.exer.2009.07.014 |
| format | Article |
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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 ∼12–17% in vessel diameters. Treatment with AAAN significantly decreased vessel diameters and venous VBF. Compared with saline AAAN produced a significant decrease of ∼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 pmolmg−1 of dry retina. The results suggest that though inhibition of nNOS decreases basal diameters, constant VBF is maintained in the retinal circulation.</description><identifier>ISSN: 0014-4835</identifier><identifier>EISSN: 1096-0007</identifier><identifier>DOI: 10.1016/j.exer.2009.07.014</identifier><identifier>PMID: 19646435</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; basal retinal blood flow ; Blood Flow Velocity - drug effects ; Blood Pressure - drug effects ; Enzyme Inhibitors - administration & dosage ; Enzyme Inhibitors - pharmacology ; Enzyme-Linked Immunosorbent Assay ; Eye ; Guanidines - pharmacology ; Heart Rate - drug effects ; imidazole ; Imidazoles - pharmacology ; Immunoassays ; Injections ; Intraocular Pressure - drug effects ; Male ; neuronal nitric oxide synthase ; NG-Nitroarginine methyl ester ; NG-Nitroarginine Methyl Ester - pharmacology ; Nitric oxide ; Nitric Oxide - metabolism ; Nitric Oxide Synthase - antagonists & inhibitors ; Nitric Oxide Synthase - metabolism ; Nitric Oxide Synthase Type I ; Nitric-oxide synthase ; Nitro Compounds - pharmacology ; Rats ; Rats, Long-Evans ; Regional Blood Flow - drug effects ; Retina ; Retinal Vessels - drug effects ; Retinal Vessels - enzymology ; Time Factors</subject><ispartof>Experimental eye research, 2009-11, Vol.89 (5), p.801-809</ispartof><rights>2009 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-11f0c3dff83537d35505368fd30f697912bd1e66b679f216bc4cbd591c938feb3</citedby><cites>FETCH-LOGICAL-c454t-11f0c3dff83537d35505368fd30f697912bd1e66b679f216bc4cbd591c938feb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.exer.2009.07.014$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19646435$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tummala, Shanti R.</creatorcontrib><creatorcontrib>Benac, Sanja</creatorcontrib><creatorcontrib>Tran, Harry</creatorcontrib><creatorcontrib>Vankawala, Anand</creatorcontrib><creatorcontrib>Zayas-Santiago, Astrid</creatorcontrib><creatorcontrib>Appel, Alyssa</creatorcontrib><creatorcontrib>Kang Derwent, Jennifer J.</creatorcontrib><title>Effects of inhibition of neuronal nitric oxide synthase on basal retinal blood flow regulation</title><title>Experimental eye research</title><addtitle>Exp Eye Res</addtitle><description>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 ∼12–17% in vessel diameters. Treatment with AAAN significantly decreased vessel diameters and venous VBF. Compared with saline AAAN produced a significant decrease of ∼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 pmolmg−1 of dry retina. The results suggest that though inhibition of nNOS decreases basal diameters, constant VBF is maintained in the retinal circulation.</description><subject>Animals</subject><subject>basal retinal blood flow</subject><subject>Blood Flow Velocity - drug effects</subject><subject>Blood Pressure - drug effects</subject><subject>Enzyme Inhibitors - administration & dosage</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Eye</subject><subject>Guanidines - pharmacology</subject><subject>Heart Rate - drug effects</subject><subject>imidazole</subject><subject>Imidazoles - pharmacology</subject><subject>Immunoassays</subject><subject>Injections</subject><subject>Intraocular Pressure - drug effects</subject><subject>Male</subject><subject>neuronal nitric oxide synthase</subject><subject>NG-Nitroarginine methyl ester</subject><subject>NG-Nitroarginine Methyl Ester - pharmacology</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - metabolism</subject><subject>Nitric Oxide Synthase - antagonists & inhibitors</subject><subject>Nitric Oxide Synthase - metabolism</subject><subject>Nitric Oxide Synthase Type I</subject><subject>Nitric-oxide synthase</subject><subject>Nitro Compounds - pharmacology</subject><subject>Rats</subject><subject>Rats, Long-Evans</subject><subject>Regional Blood Flow - drug effects</subject><subject>Retina</subject><subject>Retinal Vessels - drug effects</subject><subject>Retinal Vessels - enzymology</subject><subject>Time Factors</subject><issn>0014-4835</issn><issn>1096-0007</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUFv1DAQhS0EotvCH-ihyg0uScexY28kLlVVKFKlXuCKFdtj6lU2LnYC7b9nol2pt54sj7_3NH6PsXMODQeuLncNPmFuWoC-Ad0Al2_YhkOvagDQb9kGaFTLrehO2GkpO5oKqeV7dsJ7JZUU3Yb9ugkB3VyqFKo4PUQb55im9TbhktM0jNUU5xxdlZ6ix6o8T_PDULAiyA6FnjPOccXsmJKvwpj-0ej3Mg6r0Qf2LgxjwY_H84z9_Hrz4_q2vrv_9v366q52spNzzXkAJ3wItKvQXnQddEJtgxcQVK973lrPUSmrdB9arqyTzvqu564X24BWnLFPB9_HnP4sWGazj8XhOA4TpqUYLSTolr5P5OdXScqPQhKwFYS2B9TlVErGYB5z3A_5mSCzNmB2Zm3ArA0Y0IbiJtHF0X-xe_QvkmPkBHw5AEh5_I0kLy7i5NDHTE0Yn-Jr_v8BfueXvg</recordid><startdate>200911</startdate><enddate>200911</enddate><creator>Tummala, Shanti R.</creator><creator>Benac, Sanja</creator><creator>Tran, Harry</creator><creator>Vankawala, Anand</creator><creator>Zayas-Santiago, Astrid</creator><creator>Appel, Alyssa</creator><creator>Kang Derwent, Jennifer J.</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>200911</creationdate><title>Effects of inhibition of neuronal nitric oxide synthase on basal retinal blood flow regulation</title><author>Tummala, Shanti R. ; Benac, Sanja ; Tran, Harry ; Vankawala, Anand ; Zayas-Santiago, Astrid ; Appel, Alyssa ; Kang Derwent, Jennifer J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-11f0c3dff83537d35505368fd30f697912bd1e66b679f216bc4cbd591c938feb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>basal retinal blood flow</topic><topic>Blood Flow Velocity - drug effects</topic><topic>Blood Pressure - drug effects</topic><topic>Enzyme Inhibitors - administration & dosage</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Eye</topic><topic>Guanidines - pharmacology</topic><topic>Heart Rate - drug effects</topic><topic>imidazole</topic><topic>Imidazoles - pharmacology</topic><topic>Immunoassays</topic><topic>Injections</topic><topic>Intraocular Pressure - drug effects</topic><topic>Male</topic><topic>neuronal nitric oxide synthase</topic><topic>NG-Nitroarginine methyl ester</topic><topic>NG-Nitroarginine Methyl Ester - pharmacology</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitric Oxide Synthase - antagonists & inhibitors</topic><topic>Nitric Oxide Synthase - metabolism</topic><topic>Nitric Oxide Synthase Type I</topic><topic>Nitric-oxide synthase</topic><topic>Nitro Compounds - pharmacology</topic><topic>Rats</topic><topic>Rats, Long-Evans</topic><topic>Regional Blood Flow - drug effects</topic><topic>Retina</topic><topic>Retinal Vessels - drug effects</topic><topic>Retinal Vessels - enzymology</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tummala, Shanti R.</creatorcontrib><creatorcontrib>Benac, Sanja</creatorcontrib><creatorcontrib>Tran, Harry</creatorcontrib><creatorcontrib>Vankawala, Anand</creatorcontrib><creatorcontrib>Zayas-Santiago, Astrid</creatorcontrib><creatorcontrib>Appel, Alyssa</creatorcontrib><creatorcontrib>Kang Derwent, Jennifer J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental eye research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tummala, Shanti R.</au><au>Benac, Sanja</au><au>Tran, Harry</au><au>Vankawala, Anand</au><au>Zayas-Santiago, Astrid</au><au>Appel, Alyssa</au><au>Kang Derwent, Jennifer J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of inhibition of neuronal nitric oxide synthase on basal retinal blood flow regulation</atitle><jtitle>Experimental eye research</jtitle><addtitle>Exp Eye Res</addtitle><date>2009-11</date><risdate>2009</risdate><volume>89</volume><issue>5</issue><spage>801</spage><epage>809</epage><pages>801-809</pages><issn>0014-4835</issn><eissn>1096-0007</eissn><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 ∼12–17% in vessel diameters. Treatment with AAAN significantly decreased vessel diameters and venous VBF. Compared with saline AAAN produced a significant decrease of ∼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 pmolmg−1 of dry retina. The results suggest that though inhibition of nNOS decreases basal diameters, constant VBF is maintained in the retinal circulation.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>19646435</pmid><doi>10.1016/j.exer.2009.07.014</doi><tpages>9</tpages></addata></record> |
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| subjects | Animals basal retinal blood flow Blood Flow Velocity - drug effects Blood Pressure - drug effects Enzyme Inhibitors - administration & dosage Enzyme Inhibitors - pharmacology Enzyme-Linked Immunosorbent Assay Eye Guanidines - pharmacology Heart Rate - drug effects imidazole Imidazoles - pharmacology Immunoassays Injections Intraocular Pressure - drug effects Male neuronal nitric oxide synthase NG-Nitroarginine methyl ester NG-Nitroarginine Methyl Ester - pharmacology Nitric oxide Nitric Oxide - metabolism Nitric Oxide Synthase - antagonists & inhibitors Nitric Oxide Synthase - metabolism Nitric Oxide Synthase Type I Nitric-oxide synthase Nitro Compounds - pharmacology Rats Rats, Long-Evans Regional Blood Flow - drug effects Retina Retinal Vessels - drug effects Retinal Vessels - enzymology Time Factors |
| title | Effects of inhibition of neuronal nitric oxide synthase on basal retinal blood flow regulation |
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