title: Effects of adenosine on optic nerve head circulation in rabbits.
abstract: This study was performed to determine whether intravitreal or intravenous adenosine can alter the microcirculation in the optic nerve head (ONH) of rabbits. Capillary blood flow in the ONH was measured serially with a laser speckle tissue analyser for 2 hr after the intravitreal (0.1, 1.0 and 10 nmol) or intravenous (0.2 and 0.6 mg kg(-1)min) injections of adenosine. In addition, the effect of specific adenosine A(1) and A(2a) antagonists and an adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channel blockers on the adenosine-induced changes on the ONH blood flow was analysed. Intravitreal adenosine increased the capillary blood flow in the ONH in a dose-dependent manner, while intravenous adenosine had no effect. Co-administration of the specific adenosine A(1) receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 nmol) significantly suppressed (P=0.006, ANOVA) the increase in the ONH blood flow induced by adenosine (10 nmol). The specific A(2a) receptor antagonist, 8-(3-chlorostyryl) caffeine (CSC, 10 nmol), had a weak effect in inhibiting the increase but the change was not significant (P=0.08, ANOVA). Both specific A(1) and A(2a) receptor agonists, N(6)-cyclopentyladenosine (CPA, 10 nmol) and 2-p-(2-carboxyethyl) phenethyl-amino-5'-N-ethylcarboxamidoadenosine (CGS-21680, 10 nmol), increased the ONH tissue blood flow (P<0.01, ANOVA). Glibenclamide (10 nmol), a selective K(ATP) channels antagonist, suppressed the increase of ONH blood flow induced by 10 nmol adenosine significantly (P<0.001, ANOVA). On the other hand, 10 nmol of 8-Br-cAMP, a cAMP analog, failed to enhance the capillary blood flow in the ONH. These results indicate that adenosine increases the capillary blood flow in the ONH of rabbits, and it acts through A(1) and A(2a) receptors from the ablumenal side where pericytes are located. Activation of K(ATP) channels is strongly related to the mechanism of adenosine-induced increase in ONH blood flow, while the participation of adenylate cyclase is less likely.
authors.affiliation: Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-cho, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Hirao
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Oku
authors.forename: Wakana
authors.initials: W
authors.lastname: Goto
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Tsunehiko
authors.initials: T
authors.lastname: Ikeda
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D058916:Adenosine A1 Receptor Antagonists; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002110:Caffeine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002196:Capillaries; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D007267:Injections; D007275:Injections, Intravenous; D009898:Optic Disk / Q000098:blood supply*; D010627:Phenethylamines / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D058906:Purinergic P1 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D013268:Stimulation, Chemical; D014664:Vasodilation / Q000502:physiology*; D014822:Vitreous Body; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D000067956:Adenylyl Cyclase Inhibitors; D010627:Phenethylamines; D015221:Potassium Channels; D058906:Purinergic P1 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C081320:8-(3-chlorostyryl)caffeine; D015124:8-Bromo Cyclic Adenosine Monophosphate; D002110:Caffeine; C048599:N(6)-cyclopentyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D005905:Glyburide