Divergent roles of nitric oxide and rho kinase in vasomotor regulation of human retinal arterioles.
OBJECTIVE
Although the arteriolar segment contributes to flow regulation, there is sparse information at the single microvessel level on how vasomotor function is regulated in the human retina. The authors have previously reported vasoreactivity and its underlying mechanisms in isolated porcine retinal arterioles. Herein, they studied human retinal arterioles for comparison.


METHODS
Retinal tissues were obtained from seven patients undergoing enucleation. Human and porcine retinal arterioles were isolated and pressurized to 55 cm H(2)O luminal pressure for vasoreactivity study using videomicroscopic techniques.


RESULTS
Isolated human and porcine retinal arterioles developed myogenic tone and dilated dose dependently to bradykinin, adenosine, and sodium nitroprusside. Stepwise increases in luminal flow produced graded dilation with approximately 60% dilation at the highest flow tested. Nitric oxide (NO) synthase inhibitor L-NAME nearly abolished dilations to bradykinin and flow and attenuated the adenosine-induced dilation without altering the response to nitroprusside. Endothelin-1 caused dose-dependent constriction. Rho kinase (ROCK) inhibitor H-1152 blocked both myogenic tone and endothelin-1-induced constriction. Responses of retinal arterioles to all agonists and increased flow were similar between pigs and humans.


CONCLUSIONS
Isolated human retinal arterioles dilate to bradykinin and increased flow in an NO-dependent manner. NO contributes, in part, to adenosine-induced vasodilation. Conversely, ROCK activation mediates myogenic tone and endothelin-1-induced vasoconstriction. Similarities in these vasoactive responses and the underlying mechanisms between human and porcine retinal arterioles support the latter as a viable experimental model of the human retinal microcirculation.
Hein
Travis W
TW
Department of Ophthalmology, Scott and White Eye Institute, Temple, Texas 76504, USA. thein@tamu.edu
Rosa
Robert H
RH
Yuan
Zhaoxu
Z
Roberts
Elizabeth
E
Kuo
Lih
L
D000328:Adult; D000368:Aged; D000818:Animals; D001160:Arterioles / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D012161:Retinal Artery / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects; D054460:rho-Associated Kinases / Q000502:physiology*
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D054460:rho-Associated Kinases