Pericytes 39
vascular growth in various models of induced angiogenesis (Ruiter et al., 1993;
Ozerdem and Stallcup, 2003, 2004).
4.3 Pericytes as Regulators of Microvascular Blood Flow?
Since 1873, when Rouget regarded pericytes as contractile elements (Rouget 1874), the discussion concerning this ability has never ceased. Pericytes are likely to respond to vasoactive molecules such as nitric oxide, prostacyclin, angiotensin II, and endothelin-1, because they express respective receptors (Dehouck et al., 1997, Chakravarthy and Gardiner, 1999, Healy and Wilk, 1993). However, a prerequisite of contraction is the expression of contractile filaments of actin and myosin.
Cerebral pericytes express both smooth muscle and non-smooth muscle isoforms of actin and myosin (Herman and D’Amore, 1985). In embryonic chicken, but not in rat and mouse, all pericytes express α-SMA (Hellstrom et al., 1999). In mice, pericytes surrounding capillaries with a diameter of less than 10 µm do not show α-SMA activity, whereas pericytes of larger vessels like arterioles or post-capillary venules are regularly immune positive throughout the brain (Alliott et al., 1999;
Nehls and Drenckhahn, 1991). This may indicate functional heterogeneity, which is also supported by the strikingly different morphologies described above. In fact, considering the established interaction between endothelial cells and pericytes, it seems trivial to state that the distance from the endothelium, which varies along the vascular tree, strongly impacts on the functional state of pericytes.
Blood flow is widely believed to be regulated in precapillary arterioles, but 65%
of the noradrenergic innervation of CNS blood vessels terminate in vicinity to cap-illaries (Cohen et al., 1997). A recent study demonstrated that pericytes induce the constriction of capillaries induced by ATP and noradrenalin. Glutamate suppressed, while GABA fostered this process which could be observed through live-imaging of retinal and cerebellar slices obtained from young rats (Peppiatt et al., 2006).
40 M. Krüger and I. Bechmann
cells and juxtavascular microglia on the other, remains open. The biggest success of the last years may be the formal demonstration of their impact on capillary con-traction (Peppiatt et al., 2006). Thus, Rouget’s old idea eventually turned out to be true, albeit in an unexpected segment of the vascular tree. As we learn to observe pericytes on duty, more surprises are to come.
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