Effect of nitric oxide synthase inhibitors on endothelial [Ca2+](i) and microvessel permeability

P. He, B. Liu, F. E. Curry

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To investigate the mechanism whereby nitric oxide (NO) signaling pathways regulate microvessel permeability in vivo, we measured changes in microvessel hydraulic conductivity (L(p)) and endothelial cytoplasmic calcium concentration ([Ca2+](i)) in response to calcium ionophore, ionomycin (5 μM), and ATP (10 μM) before and after the use of NO synthase (NOS) inhibitors in single perfused frog mesenteric venular microvessels. Ionomycin induced a transient increase in endothelial [Ca2+](i) and an associated increase in L(p). The NOS inhibitors N(ω)-nitro-L-arginine methyl ester (10 and 300 μM) and N(ω)-monomethyl-L-arginine (L-NMMA; 10, 50, and 100 μM) significantly attenuated the peak increase in L(p) induced by ionomycin. A similar inhibitory effect was also observed with the increase in L(p) mediated by ATP. In contrast, D-NMMA, a biologically inactive isomer of L- NMMA, showed no effect on ionomycin-induced increase in L(p). L-Arginine (3 mM) reversed the inhibitory effect of L-NMMA 10 μM) on L(p). However, the NOS inhibitors did not alter the magnitude and time course of the biphasic increase in endothelial [Ca2+](i) induced by both ionomycin and ATP. These data suggest that 1) calcium-dependent NO release is a necessary step to increase microvessel permeability, and 2) the action of NOS inhibitors in attenuating the permeability increase in response to ionomycin and ATP occurs downstream from calcium entry and does not involve modification of the initial increase in endothelial [Ca2+](i).

Original languageEnglish (US)
Pages (from-to)H176-H185
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number1 41-1
StatePublished - 1997

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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