MUSCARINIC AGONISTS AND ANTAGONISTS CAUSE VASODILATION IN ISOLATED RAT LUNG

The present study investigated the ability of atropine and different m uscarinic receptor subtypes to affect acetylcholine (ACh)-induced bron choconstriction 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 mu M) decreased RT and precapillary and postcapillary va scular resistances and blocked ACh-induced increases in peak airway pr essure. The M(1)-selective agonist McN-A-343 (1.3 x 10(-6) M) decrease d RT from 40.27 +/- 2.98 to 29.20 +/- 2.81 cmH(2)O . l(-1). min . 100 g lung wt (P = 0.01), and ACh caused no further dilation. The M(1)-sel ective antagonist pirenzepine (1.6 x 10(-6) M) blocked ACh-induced vas odilation. The M(2)-selective antagonist gallamine (7.5 x 10(-7) M) de creased RT from 45.50 +/- 3.19 to 34.86 +/- 1.25 cmH(2)O . l(-1). min . 100 g lung wt (P < 0.05), and after gallamine, ACh further decreased RT to 28.59 +/- 1.75 cmH(2)O . l(-1). min . 100 g lung wt (P < 0.01). Neither the selective muscarinic agonists nor antagonists affected pe ak airway pressures. We conclude that ACh-induced vasodilation in isol ated rat lungs preconstricted with U-46619 is mediated by M(1) recepto rs. Atropine-induced vasodilation in this model is mediated through th e inhibition of the M(2) receptor. We postulate that this represents e ither a blockade of postganglionic receptors, permitting release of va sodilator substances from local nerve terminals, or a direct vasodilat ory effect on the vascular smooth muscle.