Functional Organization of the Retinal Microvasculature: Differential Actions of Angiotensin II Within the Feeder Vessel/Capillary Unit

摘要

Purpose: : Although decentralization is an important operational feature of the retinaa??s circulatory system, much remains to be learned about how its microvasculature is functionally organized. Here, we characterized the actions of angiotensin II within the feeder vessel/capillary unit. Methods: : Using a tissue print procedure, we isolated rat retina microvascular complexes that included a capillary network plus the feeder vessel linking it with a myocyte-encircled arteriole. A micromanipulator-controlled micropipette was used to transect isolated microvessels at the capillary/feeder vessel junction. Ionic currents and membrane capacitances were monitored via perforated-patch pipettes sealed onto abluminal cells of feeder vessels and capillaries. Calcium-imaging was used to monitor intracellular calcium in cells loaded with fura-2. Angiotensin-induced cell death was assessed by trypan blue dye exclusion. Results: : Angiotensin II activated a larger non-specific cation conductance in capillaries than in feeder vessels. Using transected retinal microvessels, we found that angiotensin (500 nM) activated a conductance of 1690 ?± 460 pS (n = 8) in capillaries and 140 ?± 50 pS (n = 6, P = 0.01) in feeder vessels. In addition, angiotensin evoked an increase in pericyte calcium of 325 ?± 20 nM (n = 81), which was markedly greater than the 55 ?± 3 nM (n = 149, P 0.0001) increase detected in proximal mural cells. Exposure to angiotensin also resulted in calcium-activated chloride currents that were larger in the capillaries (610 ?± 130 pS, n = 9) than in the feeder vessels (170 ?± 60 pS, n = 6, P = 0.01). Suggestive that angiotensin inhibits gap junction pathways in capillaries, but not feeder vessels, this vasoactive signal decreased the membrane capacitance only within the capillary network. In other experiments, we found that a 1-day exposure to 500 nM angiotensin triggered cell death in the capillary network, but not in the feeder vessels. Conclusions: : In the retinal microvasculature, angiotensin-induced changes in ionic currents, abluminal cell calcium, cell-to-cell transmission and cell viability are greater in the capillaries than in the feeder vessels. Thus, although a capillary network and its feeder vessel constitute a highly interactive operational unit (Microcirculation 14:1-10, 2007), there is functional sub-specialization within this decentralized portion of the retinaa??s circulatory system. The capillary network is the predominant site for mediating the effects of angiotensin II.