Muscarinic agonists and antagonists cause vasodilation in isolated rat lung.
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.
Wilson
P S
PS
Department of Physiology, University of South Alabama School of Medicine, Mobile 36688, USA.
Khimenko
P L
PL
Barnard
J W
JW
Moore
T M
TM
Taylor
A E
AE
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D010477:Perfusion; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011450:Prostaglandin Endoperoxides, Synthetic; D011976:Receptors, Muscarinic; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine