Microcirculatory responses to adenosine in the newborn pig retina.
The reactivity of retinal arterioles and venules to exogenous and endogenous adenosine was investigated in the newborn piglet eye in vivo. The retinal microcirculation of isoflurane-anesthetized newborn pigs was observed at 310x using videomicroscopy, and changes in the diameter of arterioles (50-100 microns in diameter) and venules (150-250 microns in diameter) occurring in response to intravitreal topical microsuffusions of various adenosinergic compounds were determined. Dose-dependent dilations of the arterioles and venules resulted from intravitreal adenosine (0.2-200 nmol) and three of its agonists: 5'-N-ethylcarboxyamidoadenosine (0.2-20 pmol), 2-chloroadenosine (0.2 pmol-2 nmol), and N6-cyclohexyladenosine (0.2 and 2.0 nmol). The resulting order of vasodilatative potency, wherein 5'-N-ethylcarboxyamidoadenosine >> 2-chloroadenosine > adenosine = N6-cyclohexyladenosine, is indicative of A2 adenosine receptor-mediated vasodilation. Significant arteriolar dilations [24 +/- 4% (p = 0.0012) and 35 +/- 5% (p = 0.0008), respectively] also resulted from intravitreal application of 0.2 nmol of iodotubercidin, an adenosine kinase inhibitor, and 0.1 nmol of nitrobenzylthioinosine, an inhibitor of adenosine reuptake/transport. The dilation induced by nitrobenzylthioinosine was blocked (p < 0.0004) by coadministration of the relatively specific A2 adenosine receptor antagonist 1,3-dipropyl-7-methylxanthine (1 nmol), confirming that nitrobenzylthioinosine induced dilation via potentiation of endogenous adenosine. Administration of 1,3-dipropyl-7-methylxanthine alone did not significantly affect arteriolar or venular diameters, suggesting that endogenous adenosine does not contribute to the maintenance of basal tone.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Neurology and Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri 63110.
J M
JM
Gidday
T S
TS
Park
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic / Q000502:physiology; D012171:Retinal Vessels / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014699:Venules / Q000187:drug effects / Q000502:physiology; D014970:Xanthines / Q000494:pharmacology
D058914:Purinergic Antagonists; D011983:Receptors, Purinergic; D014970:Xanthines; C059953:1,3-dipropyl-7-methylxanthine; D000241:Adenosine