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Sodium cromoglycate, verapamil and nicardipine antagonism to leukotriene D4 bronchoconstriction
Abstract:
1--The effects of nicardipine, verapamil and sodium cromoglycate (SCG) on the increase in pulmonary airway resistance(RAw) and decrease in pulmonary dynamic compliance (CDyn) induced by leukotriene D4 (LTD4) 0.5 micrograms kg-1 and acetylcholine (ACh) 3 micrograms kg-1 were investigated in anaesthetized guinea-pigs. The effects of these three agents on the contractile effects of LTD4 and ACh were tested on isolated tracheal preparations of the guinea-pig. 2--Nicardipine and verapamil (0.3 and 1 mg kg-1), as well as SCG (3 and 10 mg kg-1), partially but significantly inhibited the effects of LTD4 on RAw. Partial inhibition of the effect of LTD4 on CDyn was only observed with verapamil (0.3 and 1 mg kg-1). Nicardipine and verapamil had no effect on ACh-induced bronchoconstriction in vivo. 3--In concentrations higher than 10(-5) M, nicardipine and verapamil inhibited the contractile effects of LTD4 and ACh on guinea-pig isolated trachea. SCG had no effect on this preparation. 4--These results suggest that nicardipine, verapamil and SCG partially reduce the component of bronchoconstriction associated with stimulation of irritant receptors by LTD4. However, the site and mechanism of action of Ca2+-entry antagonists remain uncertain.
Insights
Nicardipine, verapamil, and sodium cromoglycate (SCG) partially inhibit leukotriene D4-induced airway resistance in guinea pigs. These drugs also inhibited leukotriene D4 and acetylcholine contractions in isolated trachea.
Area of Science:
- Pharmacology
- Respiratory Physiology
Background:
- Leukotriene D4 (LTD4) and acetylcholine (ACh) are potent bronchoconstrictors.
- Investigating the effects of calcium channel blockers and a mast cell stabilizer on airway responses is crucial for understanding asthma pathophysiology.
Purpose of the Study:
- To evaluate the inhibitory effects of nicardipine, verapamil, and sodium cromoglycate (SCG) on LTD4- and ACh-induced bronchoconstriction in vivo and in vitro.
- To explore the potential mechanisms of action of these drugs in modulating airway smooth muscle contraction.
Main Methods:
- In vivo studies in anesthetized guinea pigs measuring pulmonary airway resistance (RAw) and dynamic compliance (CDyn).
- In vitro studies using isolated guinea pig trachea to assess contractile responses to LTD4 and ACh.
- Administration of nicardipine, verapamil, and SCG at various doses.
Main Results:
- Nicardipine, verapamil, and SCG partially inhibited LTD4-induced increases in RAw.
- Verapamil, but not nicardipine or SCG, partially inhibited LTD4-induced decreases in CDyn.
- Nicardipine and verapamil inhibited LTD4- and ACh-induced contractions in isolated trachea, while SCG had no effect.
- Nicardipine and verapamil did not affect ACh-induced bronchoconstriction in vivo.
Conclusions:
- Nicardipine, verapamil, and SCG demonstrate partial efficacy in reducing LTD4-mediated bronchoconstriction, particularly the component involving irritant receptor stimulation.
- The precise site and mechanism of action for calcium-entry antagonists in this context require further investigation.