Abstract
Purpose: :
Pressure–mediated autoregulation of arterial diameter ensures smooth blood flow to an organ despite changes in systemic hemodynamics and we recently demonstrated this property in rat ophthalmic artery. The present study is focused at understanding mechanisms underlying pressure–induced constriction, myogenic tone (MT), in this artery.
Methods: :
Ophthalmic arteries (250 microns outer diameter) were isolated from Sprague–Dawley rats, cannulated with glass pipettes in an arteriograph and pressurized using a pressure myograph (Danish Myotechnology (DMT)). Changes in diameter were continuously monitored using Myoview software. Effect of a range of intraluminal pressures and different pharmacological inhibitors on MT were evaluated.
Results: :
At 70 mmHg, 29±4% (n=22) of MT was observed in less than 30 min after pressurization. Gradual increase in intraluminal pressure from 1 mmHg resulted in constriction of arteries, MT, which was maintained over pressures 50–200 mmHg, above which forced dilatation was observed. Denudation of endothelium increased sensitivity to pressure (leftward shift in the pressure–MT curves) with significant increase in MT. Phospholipase C inhibitor, U–73122, decreased myogenic tone at 70 mmHg by 37±6% and had a weaker effect on pressure–dependent increase in MT over pressures 1–150 mmHg. Similar concentration of U–73122 decreased phenylephrine–induced constriction at 10 mmHg by 64±8%. Nifedipine (1 µM) almost completely inhibited pressure–dependent activation of MT. Protein kinase C inhibitor G110963 did not affect MT over the range of pressures. Rho–kinase inhibitors, Y–27632 (1 µM) and HA 1077 (1 µM), decreased 72±4% and 73±5% of MT, respectively, at 70 mmHg and 1 µM Y–27632 strongly attenuated pressure–dependent increase in MT.
Conclusions: :
These results suggest that activation of Rho–kinase plays a dominant role in the development of MT in rat ophthalmic artery, which is in contrast to that observed in several other arteries. Maintaining myogenic tone up to a higher intraluminal pressure of 200 mmHg seems to be a unique property of ophthalmic artery and indicates efficient pressure–dependent autoregulation of ocular blood flow.
Keywords: signal transduction: pharmacology/physiology • second messengers: pharmacology/physiology • blood supply