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

Ping He, M. Zeng, F. E. Curry

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Abstract

We evaluated the role of basal nitric oxide (NO) release in the regulation of microvessel permeability under resting conditions. We measured changes in microvessel hydraulic conductivity (L(p)) and endothelial cytoplasmic calcium concentration ([Ca2+](i)) after application of NO synthase (NOS) inhibitors to the lumen of individually perfused frog mesenteric venular microvessels. NOS inhibitors caused a transient increase in L(p). The mean ratios of peak test L(p) values relative to control values in the presence of N(ω)-nitro-L-arginine methyl ester (L-NAME) at concentrations of 1, 10, and 100 μM were 2.5 ± 0.6, 2.9 ± 0.7, and 4.8 ± 0.4, respectively. N(ω)-monomethyl-L-arginine (L-NMMA) showed a similar effect and a biologically inactive isomer of L-NMMA, D-NMMA, showed no effect. These results demonstrate that basal levels of NO play a role in modulating microvessel permeability different from that due to NO produced in response to inflammatory agents. In the activated state NOS inhibitors attenuated the increased microvessel permeability in response to ionomycin and ATP [P. He, B. Liu, and F. E. Curry. Am. J. Physiol. 272 (Heart Circ. Physiol. 41): H176-H185, 1997]. The transient increase in basal permeability induced by NOS inhibitors was not accompanied by an increase in endothelial cell [Ca2+](i) and did not require the presence of extracellular calcium. Application of ketotifen, a mast cell stabilizer, and an iron-chelating reagent, deferoxamine mesylate, attenuated the transient increase in L(p) induced by L-NMMA, suggesting that basal NO may have an important antioxidant role in regulating normal permeability.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume273
Issue number2 42-2
StatePublished - Sep 26 1997

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omega-N-Methylarginine
Microvessels
Nitric Oxide Synthase
Permeability
Endothelial Cells
Nitric Oxide
Ketotifen
Calcium
Ionomycin
Deferoxamine
NG-Nitroarginine Methyl Ester
Mast Cells
Anura
Arginine
Iron
Antioxidants
Adenosine Triphosphate

All Science Journal Classification (ASJC) codes

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

Cite this

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title = "Effect of nitric oxide synthase inhibitors on basal microvessel permeability and endothelial cell [Ca2+](i)",
abstract = "We evaluated the role of basal nitric oxide (NO) release in the regulation of microvessel permeability under resting conditions. We measured changes in microvessel hydraulic conductivity (L(p)) and endothelial cytoplasmic calcium concentration ([Ca2+](i)) after application of NO synthase (NOS) inhibitors to the lumen of individually perfused frog mesenteric venular microvessels. NOS inhibitors caused a transient increase in L(p). The mean ratios of peak test L(p) values relative to control values in the presence of N(ω)-nitro-L-arginine methyl ester (L-NAME) at concentrations of 1, 10, and 100 μM were 2.5 ± 0.6, 2.9 ± 0.7, and 4.8 ± 0.4, respectively. N(ω)-monomethyl-L-arginine (L-NMMA) showed a similar effect and a biologically inactive isomer of L-NMMA, D-NMMA, showed no effect. These results demonstrate that basal levels of NO play a role in modulating microvessel permeability different from that due to NO produced in response to inflammatory agents. In the activated state NOS inhibitors attenuated the increased microvessel permeability in response to ionomycin and ATP [P. He, B. Liu, and F. E. Curry. Am. J. Physiol. 272 (Heart Circ. Physiol. 41): H176-H185, 1997]. The transient increase in basal permeability induced by NOS inhibitors was not accompanied by an increase in endothelial cell [Ca2+](i) and did not require the presence of extracellular calcium. Application of ketotifen, a mast cell stabilizer, and an iron-chelating reagent, deferoxamine mesylate, attenuated the transient increase in L(p) induced by L-NMMA, suggesting that basal NO may have an important antioxidant role in regulating normal permeability.",
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AU - He, Ping

AU - Zeng, M.

AU - Curry, F. E.

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N2 - We evaluated the role of basal nitric oxide (NO) release in the regulation of microvessel permeability under resting conditions. We measured changes in microvessel hydraulic conductivity (L(p)) and endothelial cytoplasmic calcium concentration ([Ca2+](i)) after application of NO synthase (NOS) inhibitors to the lumen of individually perfused frog mesenteric venular microvessels. NOS inhibitors caused a transient increase in L(p). The mean ratios of peak test L(p) values relative to control values in the presence of N(ω)-nitro-L-arginine methyl ester (L-NAME) at concentrations of 1, 10, and 100 μM were 2.5 ± 0.6, 2.9 ± 0.7, and 4.8 ± 0.4, respectively. N(ω)-monomethyl-L-arginine (L-NMMA) showed a similar effect and a biologically inactive isomer of L-NMMA, D-NMMA, showed no effect. These results demonstrate that basal levels of NO play a role in modulating microvessel permeability different from that due to NO produced in response to inflammatory agents. In the activated state NOS inhibitors attenuated the increased microvessel permeability in response to ionomycin and ATP [P. He, B. Liu, and F. E. Curry. Am. J. Physiol. 272 (Heart Circ. Physiol. 41): H176-H185, 1997]. The transient increase in basal permeability induced by NOS inhibitors was not accompanied by an increase in endothelial cell [Ca2+](i) and did not require the presence of extracellular calcium. Application of ketotifen, a mast cell stabilizer, and an iron-chelating reagent, deferoxamine mesylate, attenuated the transient increase in L(p) induced by L-NMMA, suggesting that basal NO may have an important antioxidant role in regulating normal permeability.

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