Abstract
Abstract: :
Purpose: Retinal hyperperfusion is a key element in the pathogenesis of a variety of retinal diseases including diabetic retinopathy (DR). The hyperperfusion is caused by a disturbance in the regulation of retinal blood flow which encompasses several mechanisms including autoregulation and vasomotion. Vasomotion is rhythmic contraction of arterioles to ensure an intermittent blood supply to adjacent microcirculatory units. Vasomotion has been shown to depend on nitric oxide (NO) in extraocular vascular beds, but the mode of regulation of vasomotion in retinal vessels is unknown. This study examines the role of NO and its intracellular mediator cyclic GMP (cGMP) in regulation of retinal vasomotion in retinal arterioles. Methods: Retinal porcine arterioles (n=61) (inner dia. 150 µm) were mounted in a small-vessel myograph for isometric recording. Vascular smooth muscle cells were loaded with Fura2-AM for measurements of intracellular free calcium. Cyclic GMP levels were decreased by inhibition of NO-synthesis with NG-Nitroarginine Methyl Ester (L-NAME) (n=6) in concentrations between 10-6-10-4 M. Cyclic GMP levels were increased either with 8-Br-cGMP (10-4-10-3.5 M) (n=6), or inhibition of phophodiesterase 5 with Zaprinast (10-8-10-5 M) (n=6). The frequency and amplitude of the vasomotion were evaluated by Fast Fourier Analysis. Results: Vasomotion was seen in 52% of the mounted vessels. L-NAME increased the frequency of the vasomotion significantly (p=0.016). 8-Br-cGMP and Zaprinast both decreased the frequency significantly (p=0.016). Neither of the drugs had a significant effect on the amplitude of vasomotion. Intracellular calcium levels followed the force pattern, with a delay of the force of 6 sec which was independent of addition of the above drugs. Conclusions: The frequency of vasomotion is increased by an L-NAME induced decrease in NO and cGMP, whereas the frequency is decreased by 8-Br-cGMP or by inhibiting cGMP breakdown using Zaprinast. The results may point to possible future ways of pharmacologic intervention in retinal diseases characterized by hyperperfusion such as diabetic retinopathy.
Keywords: blood supply • nitric oxide