CAN LOW-DENSITY-LIPOPROTEIN INFLUENCE MICROVASCULAR CALIBER

The intracellular free calcium concentration ([Ca2+](i)) plays an impo rtant role in the regulation of vascular tone. In vascular smooth musc le cells (VSMCs) LDL causes changes in vascular tone by increasing [Ca 2+](i). Pericytes are regarded as the microvascular counterpart of VSM Cs and implicated in the regulation of microvascular cell biology unde r normal and pathological conditions (e.g., diabetes mellitus, arteria l hypertension, arteriosclerosis). For this reason pericytes and VSMCs were compared in their ability to increase [Ca2+](i) after stimulatio n with LDL. Single VSMCs and pericytes were loaded with 2 mu M of the Ca2+-sensitive dye Indo-1/AM. Fluorescence was recorded at 405 nm (Ca2 +-bound) and 485 nn (Ca2+-free). Cells in suspension were loaded with 2 mu M of the calcium ionophore FURA-2 AM (excitation wavelengths: 340 and 380 nn, emission 505 nm). Basal [Ca2+](i) levels were significant ly higher in single pericytes (165 +/- 38 nmol/L, n = 41) than in VSMC s (150 +/- 39 nmol/L, n = 40, P = 0.0038). In cell suspensions the fol lowing values were obtained: Pericytes (113 +/- 27 nmol/L, n = 36) and VSMCs (109 +/- 26 nmol/L, n = 28), which are statistically not signif icant. For all concentrations of LDL used (except at 1 mu g/ml n-LDL), the increase above basal values was significant and both cell types s howed a clear dose-dependent reaction pattern. This study shows for th e first time that pericytes and VSMCs increase their [Ca2+](i) in a si milar way after LDL stimulation. In analogy to aortic smooth muscle ce lls, our results indicate that LDL mediated [Ca2+]i changes in pericyt es in the microvascular bed may cause vasoconstriction leading to impa irment of blood now in the microvasculature. (C) 1998 Academic Press.