title: Nitric oxide dilates rat retinal blood vessels by cyclooxygenase-dependent mechanisms.
abstract: It has been suggested that nitric oxide (NO) stimulates the cyclooxygenase (COX)-dependent mechanisms in the ocular vasculature; however, the importance of the pathway in regulating retinal circulation in vivo remains to be elucidated. Therefore, we investigated the role of COX-dependent mechanisms in NO-induced vasodilation of retinal blood vessels in thiobutabarbital-anesthetized rats with and without neuronal blockade (tetrodotoxin treatment). Fundus images were captured with a digital camera that was equipped with a special objective lens. The retinal vascular response was assessed by measuring changes in diameter of the retinal blood vessel. The localization of COX and soluble guanylyl cyclase in rat retina was examined using immunohistochemistry. The NO donors (sodium nitroprusside and NOR3) increased the diameter of the retinal blood vessels but decreased systemic blood pressure in a dose-dependent manner. Treatment of rats with indomethacin, a nonselective COX inhibitor, or SC-560, a selective COX-1 inhibitor, markedly attenuated the vasodilation of retinal arterioles, but not the depressor response, to the NO donors. However, both the vascular responses to NO donors were unaffected by the selective COX-2 inhibitors NS-398 and nimesulide. Indomethacin did not change the retinal vascular and depressor responses to hydralazine, 8-(4-chlorophenylthio)-guanosine-3', 5'-cyclic monophosphate (a membrane-permeable cGMP analog) and 8-(4-chlorophenylthio)-adenosine-3', 5'-cyclic monophosphate (a membrane-permeable cAMP analog). Treatment with SQ 22536, an adenylyl cyclase inhibitor, but not ODQ, a soluble guanylyl cyclase inhibitor, significantly attenuated the NOR3-induced vasodilation of retinal arterioles. The COX-1 immunoreactivity was found in retinal blood vessels. The retinal blood vessel was faintly stained for soluble guanylyl cyclase, although the apparent immunoreactivities on mesenteric and choroidal blood vessels were observed. These results suggest that NO exerts a substantial part of its dilatory effect via a mechanism that involves COX-1-dependent pathway in rat retinal vasculature.
authors.affiliation: Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, Tokyo, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Ogawa
authors.forename: Asami
authors.initials: A
authors.lastname: Mori
authors.forename: Masami
authors.initials: M
authors.lastname: Hasebe
authors.forename: Maya
authors.initials: M
authors.lastname: Hoshino
authors.forename: Maki
authors.initials: M
authors.lastname: Saito
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakahara
authors.forename: Kunio
authors.initials: K
authors.lastname: Ishii
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000779:Anesthetics, Local / Q000008:administration & dosage; D000818:Animals; D001160:Arterioles / Q000201:enzymology; D001794:Blood Pressure; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006339:Heart Rate; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism; D012171:Retinal Vessels / Q000187:drug effects / Q000201:enzymology*; D000071756:Soluble Guanylyl Cyclase; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage; D014699:Venules / Q000201:enzymology
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D000779:Anesthetics, Local; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D020030:Nitric Oxide Donors; D018160:Receptors, Cytoplasmic and Nuclear; D014665:Vasodilator Agents; D009569:Nitric Oxide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase