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Kawamura, H. et al. Effects of angiotensin II on the pericyte-containing microvasculature of the rat retina. J. Physiol. (Lond.) 561, 671-683

Department of Ophthalmology and Visual Sciences, University of Michigan, 1000 Wall Street, Ann Arbor, MI 48105, USA.
The Journal of Physiology (Impact Factor: 4.54). 01/2005; 561(Pt 3):671-83. DOI: 10.1113/jphysiol.2004.073098
Source: PubMed

ABSTRACT The aim of this study was to identify the mechanisms by which angiotensin II alters the physiology of the pericyte-containing microvasculature of the retina. Despite evidence that this vasoactive signal regulates capillary perfusion by inducing abluminal pericytes to contract and thereby microvascular lumens to constrict, little is known about the events linking angiotensin exposure with pericyte contraction. Here, using microvessels freshly isolated from the adult rat retina, we monitored pericyte currents via perforated-patch pipettes, measured pericyte calcium levels with fura-2 and visualized pericyte contractions and lumen constrictions by time-lapse photography. We found that angiotensin activates nonspecific cation (NSC) and calcium-activated chloride channels; the opening of these channels induces a depolarization that is sufficient to activate the voltage-dependent calcium channels (VDCCs) expressed in the retinal microvasculature. Associated with these changes in ion channel activity, intracellular calcium levels rise, pericytes contract and microvascular lumens narrow. Our experiments revealed that an influx of calcium through the NSC channels is an essential step linking the activation of AT(1) angiotensin receptors with pericyte contraction. Although not required in order for angiotensin to induce pericytes to contract, calcium entry via VDCCs serves to enhance the contractile response of these cells. In addition to activating nonspecific cation, calcium-activated chloride and voltage-dependent calcium channels, angiotensin II also causes the functional uncoupling of pericytes from their microvascular neighbours. This inhibition of gap junction-mediated intercellular communication suggests a previously unappreciated complexity in the spatiotemporal dynamics of the microvascular response to angiotensin II.

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    • "The way in during which central innervation and local vasoactive signals regulate pericyte tone in vivo, however, remains poorly understood. Studies of retinal capillaries suggest that pericytes react to intrinsic signaling in much the same way as smooth muscle cells: Pericyte constrictions have hence been observed in response to mechanical stretch and exposure to angiotensin II (via AT1 receptors) [55] and endothelin-1 (via ETA receptors) [91], by a Ca++ dependent mechanism [25]. Meanwhile, pericytes relax in response to adenosine [68], ATP [56], and nitric oxide (NO) [37, 38], as well as to cholinergic [117] and adrenergic (via β2 receptors) [25] stimulation. "
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    • "First, CTTH might, in theory, be reduced by reversing capillary constrictions caused by pericytes. Pericytes have been reported to constrict in response to stimulation of b 2 -adrenergic receptors (Zschauer et al., 1996), AT 1 angiotensin II receptors (Kawamura et al., 2004; Matsugi et al., 1997), and endothelin-1 receptors (Dehouck et al., 1997) via a calcium channel-dependent mechanism in vitro. Blockage of specific receptor systems that can cause widespread pericyte constriction would therefore be expected to reduce CTTH and upstream neurovascular dysfunction. "
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    • "The presence of pericytes along microvessels and their contractile capabilities was 'however' revealed in the late 19th and early 20th centuries (Rouget 1879, Krogh 1929), although this was largely overlooked until more recently (Pallone 1994, Pallone & Silldorff 2001, Pallone & Mattson 2002, Kawamura et al. 2004, Peppiatt et al. 2006, Puro 2007, Crawford et al. 2011, 2012). Pericytes are singular smooth muscle-like cells residing on the abluminal side of the endothelium. "
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