Nicotine impairs histamine-induced increases in macromolecular efflux

Role of oxygen radicals

William Mayhan, Glenda M. Sharpe

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Nicotine, a major component of cigarettes and smokeless tobacco, has toxic effects on endothelium and impairs reactivity of resistance arterioles in response to agonists that stimulate the synthesis and/or release of nitric oxide. However, the effect of nicotine on nitric oxide synthase-dependent increases in macromolecular transport is not known. Thus our first goal was to determine the effect of nicotine on histamine-induced increases in macromolecular efflux. We used intravital microscopy and FITC dextran (mol wt 70,000) (FITC-dextran-70K) to examine macromolecular extravasation from postcapillary venules in response to histamine before and after intravenous infusion of vehicle or nicotine. Extravasation of macromolecules was quantitated by counting venular leaky sites and calculating clearance (ml/s x 10-6) of FITC-dextran-70K. Histamine elicited reproducible increases in venular leaky sites and clearance in hamsters infused with vehicle. In contrast, nicotine infusion inhibited histamine-induced increases in macromolecular efflux. Histamine (1.0 and 5.0 μM) elicited 19 ± 2 and 34 ± 4 vs. 3 ± 1 and 11 ± 5 leaky sites per 0.11 cm2, before vs. after nicotine infusion, respectively (P < 0.05). Histamine-induced clearance of FITC- dextran-70K was also impaired after infusion of nicotine. Our second goal was to examine whether alterations in histamine-induced increases in macromolecular efflux by nicotine may be related to the production of oxygen radicals. Application of superoxide dismutase (150 U/ml) to the hamster cheek pouch restored histamine-induced increases in venular leaky sites and clearance of FITC-dextran-70K during infusion of nicotine. Thus nicotine alters agonist-induced increases in microvascular permeability, via the formation of oxygen radicals, to presumably inactivate nitric oxide.

Original languageEnglish (US)
Pages (from-to)1589-1595
Number of pages7
JournalJournal of Applied Physiology
Volume84
Issue number5
StatePublished - May 1 1998

Fingerprint

Nicotine
Histamine
Reactive Oxygen Species
Cricetinae
Nitric Oxide
Smokeless Tobacco
Venules
Cheek
Poisons
Capillary Permeability
Arterioles
Intravenous Infusions
Nitric Oxide Synthase
Tobacco Products
Superoxide Dismutase
Endothelium
fluorescein isothiocyanate dextran

Keywords

  • Fluorescein isothiocyanate-dextran
  • Hamsters
  • Nitric oxide
  • Superoxide dismutase
  • Vascular permeability
  • Venules

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Nicotine impairs histamine-induced increases in macromolecular efflux : Role of oxygen radicals. / Mayhan, William; Sharpe, Glenda M.

In: Journal of Applied Physiology, Vol. 84, No. 5, 01.05.1998, p. 1589-1595.

Research output: Contribution to journalArticle

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abstract = "Nicotine, a major component of cigarettes and smokeless tobacco, has toxic effects on endothelium and impairs reactivity of resistance arterioles in response to agonists that stimulate the synthesis and/or release of nitric oxide. However, the effect of nicotine on nitric oxide synthase-dependent increases in macromolecular transport is not known. Thus our first goal was to determine the effect of nicotine on histamine-induced increases in macromolecular efflux. We used intravital microscopy and FITC dextran (mol wt 70,000) (FITC-dextran-70K) to examine macromolecular extravasation from postcapillary venules in response to histamine before and after intravenous infusion of vehicle or nicotine. Extravasation of macromolecules was quantitated by counting venular leaky sites and calculating clearance (ml/s x 10-6) of FITC-dextran-70K. Histamine elicited reproducible increases in venular leaky sites and clearance in hamsters infused with vehicle. In contrast, nicotine infusion inhibited histamine-induced increases in macromolecular efflux. Histamine (1.0 and 5.0 μM) elicited 19 ± 2 and 34 ± 4 vs. 3 ± 1 and 11 ± 5 leaky sites per 0.11 cm2, before vs. after nicotine infusion, respectively (P < 0.05). Histamine-induced clearance of FITC- dextran-70K was also impaired after infusion of nicotine. Our second goal was to examine whether alterations in histamine-induced increases in macromolecular efflux by nicotine may be related to the production of oxygen radicals. Application of superoxide dismutase (150 U/ml) to the hamster cheek pouch restored histamine-induced increases in venular leaky sites and clearance of FITC-dextran-70K during infusion of nicotine. Thus nicotine alters agonist-induced increases in microvascular permeability, via the formation of oxygen radicals, to presumably inactivate nitric oxide.",
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