Mechanisms of airway hypercontractility in basenji-greyhound dogs.
The comparative effects of contractile agonists and physiological stimulation of the tracheal and bronchial smooth muscle (BSM) response were studied isometrically in situ in five Basenji-greyhound (BG) and six mongrel dogs. Frequency-response curves generated by bilateral stimulation of the vagus nerves (0-20 Hz, 15-20 V, 2-ms duration) elicited greater maximal contraction in mongrel trachea (36.8 +/- 8.1 vs. 26.9 +/- 4.0 g/cm; P less than 0.02) and exhibited greater responsiveness in mongrel BSM (half-maximal response to electrical stimulation 3.0 +/- 1.1 vs. 7.0 +/- 0.5 Hz; P less than 0.05) compared with BG dogs. However, muscarinic sensitivity to intravenous methacholine (MCh) was substantially greater in BG dogs; MCh caused contraction greater than 1.5 g/cm at a mean dose of 3.0 X 10(-10) mol/kg for BG dogs compared with 5.1 X 10(-9) mol/kg for mongrel controls (P less than 0.03, Mann-Whitney rank-sum test). In contrast to the muscarinic response, the contractile response elicited by intravenous norepinephrine after beta-adrenergic blockade was similar in trachea and bronchus for both mongrel and BG dogs. Our data confirm previous in vitro demonstration of tracheal hyporesponsiveness in BG dogs and demonstrate that the contraction resulting from efferent parasympathetic stimulation is less in the BG than mongrel dogs. However, postsynaptic muscarinic responsiveness of BG BSM is substantially increased. We conclude that a component of airway responsiveness in BG dogs depends directly on contractile forces generated postsynaptically that are nongeometry dependent, postjunctional, and agonist specific.
Murphy, TM; Munoz, NM; Hirshman, CA; Blake, JS; Leff, AR
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