Pulmonary effects of endogenous and exogenous nitric oxide in the pig: relation to cigarette smoke inhalation

Br J Pharmacol. 1993 Oct;110(2):739-46. doi: 10.1111/j.1476-5381.1993.tb13874.x.

Abstract

1. Pentobarbitone-anaesthetized pigs were challenged with cigarette smoke (unfiltered or filtered through a Cambridge glass fibre filter to remove the particulate phase including nicotine), as well as nicotine aerosol and the gas phase components nitric oxide (NO) and carbon monoxide (CO); the effects on the bronchial and pulmonary circulations, and pulmonary airway mechanics, were examined. The relative importance of endogenous NO mechanisms in the pig lung was also studied by giving the NO synthesis inhibitor NG-nitro-L-arginine (L-NOARG; 50 mg kg-1) intravenously. Mean arterial pressure and blood flow in the bronchial, pulmonary and femoral circulations were measured, the latter with ultrasonic flow probes around the supplying arteries, and vascular resistance (VR) was calculated. Changes in pulmonary airways resistance (Rpulm) and lung dynamic compliance (Cdyn) were also determined. Finally, the concentration of NO in inhaled air during cigarette smoke and NO gas challenges was continuously monitored by a chemiluminescence method and the relative contribution of NO in cigarette smoke-induced vascular effects in the pig lung was calculated. 2. Cigarette smoke challenge, with or without a Cambridge filter, caused a rapid vasodilator response in the bronchial circulation and the major part (75%) of this response was probably caused by NO present in smoke. NO challenge caused profound bronchial vasodilation with dose-response characteristics between 10 and 100 p.p.m. The small part of the cigarette smoke-induced response not explained by the NO content may be caused by CO, showing weak vasodilator effect in the bronchial circulation. The L-NOARG-induced relative increase in bronchial VR was 2-3 times higher than the changes in pulmonary, femoral and systemic VR, suggesting a strong influence of endothelial NO mechanisms on basal tone in the bronchial circulation.3. Challenge with unfiltered cigarette smoke induced variable responses in the pulmonary circulation,whereas inhalation of filtered smoke caused consistent pulmonary vasodilatation. The major part of this vasodilator response was probably caused by NO, which was a potent dilator of the pulmonary circulation with maximal effect achieved with as little as 10 p.p.m. The effect of NO may be opposed in unfiltered smoke by the particulate phase (but not nicotine), presumably by inducing sympathetic reflexes. L-NOARG caused similar relative increases in pulmonary, femoral and systemic VR.4. Cigarette smoke inhalation induced bronchodilatation in the pentobarbitone-anaesthetized pig as revealed by changes in Rpulm and Cdyn. Both NO and nicotine may contribute to this response. NO inhalation reduced Rpulm in the basal state with maximal effect at 30 p.p.m. The mechanism for NO-induced bronchodilatation may be indirect in the pig, since pretreatment with L-NOARG blocked the response. L-NOARG did not affect basal Rpulm.5. In conclusion, bronchial vasodilatation caused by continuous cigarette smoke inhalation in the pig,seems to be largely mediated (approximately 75%) by NO. The remaining part could be mediated by CO. Cigarette smoke particles, but not nicotine, may counteract NO-induced relaxation in the pulmonary circulation, thus resulting in variable effects in the pulmonary circulation during challenge with unfiltered cigarette smoke. NO also acts as a bronchodilator in the pig, but the mechanism may be indirect. Finally, endogenous NO mechanisms appear to be strongly involved in the control of basal tone in the bronchial circulation, less so in the pulmonary circulation and not at all in bronchial smooth muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Bronchodilator Agents / pharmacology
  • Carbon Monoxide / pharmacology
  • Chlorisondamine / pharmacology
  • Female
  • Hemodynamics / drug effects
  • Male
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Nicotine / pharmacology
  • Nitric Oxide / analysis
  • Nitric Oxide / pharmacology*
  • Nitric Oxide / physiology*
  • Nitroarginine
  • Nitrous Oxide / pharmacology
  • Plants, Toxic
  • Pulmonary Circulation / drug effects*
  • Smoke / analysis
  • Smoking / physiopathology*
  • Swine
  • Tobacco / chemistry
  • Vasodilation / drug effects
  • Vasodilator Agents / pharmacology

Substances

  • Bronchodilator Agents
  • Smoke
  • Vasodilator Agents
  • Nitroarginine
  • Nitric Oxide
  • Nicotine
  • Carbon Monoxide
  • Arginine
  • Chlorisondamine
  • Nitrous Oxide