KATP channels mediate adenosine-induced hyperemia in retina.
OBJECTIVE
The authors and others have shown previously that the purine nucleoside adenosine is a potent vasodilator in the retinal microcirculation, mediating increases in retinal blood flow (RBF) in response to several autoregulatory stimuli. The current experiments were undertaken to elucidate the involvement of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels and the adenylate cyclase--cyclic adenosine monophosphate (cAMP) second-messenger system in the transduction of adenosine's hyperemic response.


METHODS
Retinal fluorescein angiograms were videorecorded in isoflurane-anesthetized newborn pigs, and changes in arteriovenous transit times and retinal arteriolar and venular diameters were used to estimate stimulus-induced changes in RBF.


RESULTS
Intravitreal perivascular microsuffusion of 5 nmol and 50 nmol adenosine caused dose-dependent increases in RBF of 79% +/- 4% (P < 0.05; n = 5) and 323% +/- 61% (P < 0.05; n = 5), respectively. The KATP channel antagonist glibenclamide (0.5 nmol and 5 nmol) caused a significant, dose-dependent attenuation of the hyperemic response to 5 nmol adenosine. The specificity of glibenclamide for blocking KATP channels was demonstrated by its ability to block by 94% +/- 6% (P < 0.05; n = 5) the increase in RBF (94% +/- 7%; P < 0.05) elicited by the intravitreal microsuffusion of the KATP channel agonist cromakalim (5 nmol), whereas it had no effect on the 103% +/- 12% increase in RBF (P < 0.05; n = 5) induced by the nitric oxide donor sodium nitroprusside (15 nmol). Adenosine-induced hyperemia was not potentiated by forskolin (1.7 nmol; n = 4), an adenylate cyclase activator, and was not attenuated by dideoxyadenosine (5 nmol; n = 4), an adenylate cyclase inhibitor. In addition, no significant increases in RBF could be elicited by 2.5 to 25 nmol 8-bromo-cAMP (n = 4), a membrane-permeable cAMP analog.


CONCLUSIONS
These results in the piglet indicate that adenosine increases blood flow in the retina by activating KATP channels, not by increasing in cyclic AMP secondary to adenylate cyclase activation. They also underscore the potential importance of KATP channels in the transduction of retinal vasodilatative responses to other agonists.
Gidday
J M
JM
Department of Neurology and Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Maceren
R G
RG
Shah
A R
AR
Meier
J A
JA
Zhu
Y
Y
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000502:physiology*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D019806:Cromakalim; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005451:Fluorescein Angiography; D005905:Glyburide / Q000494:pharmacology; D006940:Hyperemia / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D012171:Retinal Vessels / Q000503:physiopathology*; D015290:Second Messenger Systems; D015398:Signal Transduction; D013552:Swine; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000241:Adenosine; D005905:Glyburide