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H. Kawamura, Q. Li, M. Kobayashi, D.M. Wu, D.G. Puro; Angiotensine-induced Changes in the Physiology of Pericyte-containing Retinal Microvessels . Invest. Ophthalmol. Vis. Sci. 2003;44(13):336.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Angiotensin II (Ang II) is a putative vasoactive molecule in the retina. However, knowledge of the mechanisms by which Ang II regulates the function of the retinal microvasculature is limited. Here we assess the effects of Ang II on the ionic currents, intracellular calcium levels and contractility of pericyte-containing retinal microvessels. Methods: Retinas from adult rats were incubated in a papain-containing solution and then pressed gently between two glass coverslips so that microvessels adhered to the glass. Experiments were done within 3 hrs. Ionic currents were monitored in pericytes via perforated-patch pipettes; the calcium concentration ([Ca2+]i) of pericytes was quantified using fura-2, and microvascular contractions were visualized with the aid of time-lapse photography. Results: Exposure of freshly isolated retinal microvessels to Ang II reversibly activated a depolarizing non-specific cationic conductance. The relative permeability of this conductance was PCa:PNa:PK = 3:1:1. In addition, calcium-activated chloride currents were activated. Electrophysiological experiments also revealed that after ~1 min of exposure to Ang II, the electrotonic coupling of pericytes to neighboring microvascular cells decreased dramatically by a mechanism that was sensitive to the PKC inhibitor, chelerythrine. Calcium imaging revealed that Ang-exposure increased [Ca2+]i by activating calcium release and influx. Associated with these changes, pericytes contracted and adjacent capillary lumens constricted. Conclusions: Ang II activates calcium-permeable non-specific cationic channels, increases pericyte calcium levels and causes pericyte contractions in retinal microvessels. In addition to effects on individual microvascular cells, the inhibition of cell-to-cell communication within retinal capillaries may be an important, previously unrecognized, action of Ang II. CR: None.
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