Related Experiment Video
Updated: Jul 6, 2026

In vitro Measurements of Tracheal Constriction Using Mice
Published on: June 25, 2012
Human meconium has a pulmonary vascular and airway smooth muscle relaxant effect
Rogerio Tessler1, Jingyi Pan, Humberto Holmer Fiori
1Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
Abstract:
Meconium aspiration is believed to cause persistent pulmonary hypertension syndrome of the newborn (PPHN) via vasoconstriction, whereas meconium has a relaxant effect on rat tracheal muscle. We evaluated the meconium effect on lung vascular and airway muscle. Three-days old and adult rat 3rd-4th generation arteries and adjacent bronchi were studied in vitro. Fresh homogenized meconium did not induce arterial or airway muscle contraction. In precontracted arteries, meconium induced muscle relaxation that was greater (p < 0.01) in the newborn (53 +/- 5%), when compared with adult vessels (34 +/- 3%). This relaxant response was partially abrogated (p < 0.01) by L-NAME (28 +/- 4%) and enhanced by a superoxide scavenger (55 +/- 4%). Precontracted bronchial muscle relaxed to meconium in vitro and the magnitude of response was greater in the adult when compared with the newborn (p < 0.01). In vitro incubation with meconium (3 h) reduced agonist-stimulated force and enhanced endothelium-dependent relaxation (p < 0.01). Airway meconium instillation followed by mechanical ventilation enhanced thromboxane-induced newborn rat pulmonary arterial muscle contraction in vitro (p < 0.01). We conclude that meconium is a pulmonary vasodilator in vitro Meconium is first noted to be present at 12 wk gestation in humans. It is the by-product of fetal amniotic fluid, lanugo, skin cells, and vernix caseosa swallowing, as well it contains cells derived from the gastrointestinal tract (). Meconium composition also includes four different biliary acids (cholic, chenodeoxycholic, deoxycholic, and lithocholic) and minerals of which copper, zinc, magnesium, calcium iron, and phosphorus are the most common (). In addition, it contains plasmatic proteins such as alpha1-antitripsin and phospholipase A2 (4,5).
Insights
Meconium acts as a pulmonary vasodilator in newborn rat lungs, contrary to previous beliefs. This study found meconium relaxes lung vascular and airway muscles in vitro.
Area of Science:
- Neonatal Physiology
- Pulmonary Medicine
- Gastroenterology
Background:
- Meconium aspiration is linked to persistent pulmonary hypertension syndrome of the newborn (PPHN), often attributed to vasoconstriction.
- However, meconium has demonstrated a relaxant effect on rat tracheal muscle in previous studies.
Purpose of the Study:
- To investigate the in vitro effects of meconium on both lung vascular and airway smooth muscle in newborn and adult rats.
- To clarify the role of meconium in pulmonary vascular tone and airway reactivity.
Main Methods:
- Isolated third-to-fourth generation pulmonary arteries and bronchi from 3-day-old and adult rats were studied.
- Vascular and airway muscle responses to meconium were assessed in vitro, with and without pre-contraction, and in the presence of L-NAME and a superoxide scavenger.
- The impact of meconium incubation on agonist-stimulated force and endothelium-dependent relaxation was evaluated.
- In vivo meconium instillation followed by mechanical ventilation was performed, with subsequent in vitro assessment of pulmonary arterial muscle contraction.
Main Results:
- Fresh homogenized meconium did not induce contraction in arterial or airway smooth muscle.
- Meconium induced significant relaxation in precontracted pulmonary arteries, with a greater effect in newborn rats (53%) compared to adults (34%).
- This relaxation was partially inhibited by L-NAME and enhanced by a superoxide scavenger, suggesting a role for nitric oxide and superoxide.
- Bronchial smooth muscle relaxation to meconium was greater in adult rats than in newborns.
- In vitro meconium incubation reduced agonist-induced force and enhanced endothelium-dependent relaxation.
- Airway meconium instillation in vivo increased pulmonary arterial muscle contraction in response to thromboxane.
Conclusions:
- Meconium acts as a pulmonary vasodilator in vitro, challenging the traditional view of its role in PPHN.
- The relaxant effect on pulmonary vasculature is age-dependent and involves nitric oxide and superoxide pathways.
- While meconium relaxes airway smooth muscle, in vivo instillation can lead to increased pulmonary arterial reactivity.
Related Concept Videos
Direct-Acting Cholinergic Agonists: Pharmacological Actions
Cholinergic Antagonists: Therapeutic Uses
Respiratory Tract: Ipratropium, aclidinium, and tiotropium treat asthma, chronic bronchitis, and chronic obstructive pulmonary disease (COPD). They protect against bronchoconstriction caused by irritants like cigarette smoke, sulfur dioxide, and ozone. They also help reduce nasopharyngeal secretions in common...
Cholinergic Antagonists: Pharmacological Actions
Gastrointestinal Effects: Antimuscarinics reduce gut contractions, increase gastric emptying, and slow intestinal transit. They partly inhibit gastric acid secretion...
Antiasthma Drugs: Muscarinic Receptor Antagonists
Antimuscarinic agents compete with ACh for the same binding site on the muscarinic receptors. By binding to these receptors, they inhibit the downstream effects of ACh and block the parasympathetic...
Upper Respiratory Drugs: Antitussives, Expectorants, and Mucolytics
Antitussives include codeine, dextromethorphan (Robitussin), and benzonatate (Tessalon). Codeine and dextromethorphan exert their effects centrally by suppressing the cough reflex center in the medulla. Benzonatate operates peripherally within the respiratory tract by anesthetizing...
Skeletal Muscle Relaxants: Therapeutic Uses
