Muscarinic agonists and antagonists cause vasodilation in isolated rat lung

Abstract

The present study investigated the ability of atropine and different muscarinic receptor subtypes to affect acetylcholine (ACh)-induced bronchoconstriction and vasodilation in the isolated rat lung model. ACh (10(-7) M) given after U-46619 decreased total (RT), precapillary, and postcapillary vascular resistances and increased peak airway pressure. Atropine (20 microM) decreased RT and precapillary and postcapillary vascular resistances and blocked ACh-induced increases in peak airway pressure. The M1-selective agonist McN-A-343 (1.3 x 10(-5) M) decreased RT from 40.27 +/- 2.98 to 29.20 +/- 2.81 cmH2O.l–1.min-100 g lung wt (P = 0.01), and ACh caused no further dilation. The M1-selective antagonist pirenzepine (1.6 x 10(-6) M) blocked ACh-induced vasodilation. The M2-selective antagonist gallamine (7.5 x 10(-7) M) decreased RT from 45.50 +/- 3.19 to 34.86 +/- 1.25 cmH2O.l–1.min.100 g lung wt (P < 0.05), and after gallamine, ACh further decreased RT to 28.59 +/- 1.75 cmH2O.l–1.min.100 g lung wt (P < 0.01). Neither the selective muscarinic agonists nor antagonists affected peak airway pressures. We conclude that ACh-induced vasodilation in isolated rat lungs preconstricted with U-46619 is mediated by M1 receptors. Atropine-induced vasodilation in this model is mediated through the inhibition of the M2 receptor. We postulate that this represents either a blockade of postganglionic receptors, permitting release of vasodilator substances from local nerve terminals, or a direct vasodilatory effect on the vascular smooth muscle.