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.

Pediatric Research
|March 25, 2008
PubMed

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 Actions00:59

Direct-Acting Cholinergic Agonists: Pharmacological Actions

Direct-acting cholinergic agonists exert their pharmacological actions by mimicking the effects of acetylcholine on postsynaptic muscarinic receptors to generate parasympathetic responses. These agents elicit a range of physiological responses, including cardiovascular effects. For example, activation of muscarinic receptors induces bradycardia, decreased cardiac output, reduced peripheral resistance, and consequent hypotension. In the eye, stimulation of M3 receptors leads to smooth muscle...
Cholinergic Antagonists: Therapeutic Uses01:26

Cholinergic Antagonists: Therapeutic Uses

Antimuscarinic drugs have various therapeutic applications by inhibiting parasympathetic stimulation in different systems. Here are the key therapeutic uses of antimuscarinics:    
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 Actions01:28

Cholinergic Antagonists: Pharmacological Actions

Antimuscarinic drugs block muscarinic receptors in multiple systems, including the gut, eye, smooth muscles, respiratory tract, cardiovascular, and central nervous systems. They produce similar effects with varying selectivity depending on the specific agent and tissue. Here are the key pharmacological actions of antimuscarinics:
Gastrointestinal Effects: Antimuscarinics reduce gut contractions, increase gastric emptying, and slow intestinal transit. They partly inhibit gastric acid secretion...
Antiasthma Drugs: Muscarinic Receptor Antagonists01:20

Antiasthma Drugs: Muscarinic Receptor Antagonists

Muscarinic receptor antagonists, also known as antimuscarinic agents, are a class of bronchodilators used to treat asthma, although they are more commonly used to treat COPD. They work by inhibiting the action of acetylcholine (ACh), a neurotransmitter, on muscarinic receptors found in the airways.
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 Mucolytics01:23

Upper Respiratory Drugs: Antitussives, Expectorants, and Mucolytics

Respiratory symptoms, such as congestion and cough, commonly accompany respiratory tract conditions. Various medications, such as antitussives, expectorants, and mucolytics, play crucial roles in providing relief.
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 Uses01:31

Skeletal Muscle Relaxants: Therapeutic Uses

Skeletal muscle relaxants are used to relax muscle tone and alleviate painful muscle contractions. However, the choice of skeletal muscle relaxants depends on the duration of the surgical procedure in order to minimize potential side effects. Skeletal muscle relaxants like neuromuscular blocking agents [NMBAs] are commonly employed as adjuvants alongside general anesthetics in clinical settings. NMBAs are also used to maintain controlled ventilation during surgery of the larynx or pharynx as...