Physiological antagonism caused by adrenergic stimulation of canine tracheal muscle.
We studied the simultaneous alpha- and beta-adrenergic response characteristics of canine tracheal smooth muscle in 398 strips from 67 dogs in vitro. Experiments were performed to determine the effects of beta-adrenergic blockade on the expression of the alpha-adrenoceptor contractile responses elicited by norepinephrine (NE), phenylephrine (PE), and clonidine (CLO). Maximal active tension caused by NE increased from 39.1 +/- 27.0 to 241 +/- 75.0 g/cm2 as the concentration of propranolol (PROP) was increased from 10(-6) to 10(-4) M. Augmentation of tracheal smooth muscle contraction caused by PE and CLO was also observed with progressive beta-adrenoceptor blockade; contraction to NE, PE, and CLO was blocked selectively with 3 X 10(-5) M phentolamine (PA) and phenoxybenzamine (PBZ). The beta-adrenergic relaxing properties of the same three agonists were also studied. After alpha-adrenergic blockade with PA or PBZ, all three agonists caused relaxation (NE greater than CLO greater than PE) of methacholine-induced contraction of tracheal smooth muscle that was reversed selectively with PROP. We demonstrate that NE, PE, and CLO cause simultaneous stimulation of both the alpha- and beta-adrenergic receptors in tracheal smooth muscle; the net response elicited is the result of adrenergic physiological antagonism and depends on the relative degree of alpha- and/or beta-adrenoceptor blockade.
Leff
A R
AR
Tallet
J
J
Munoz
N M
NM
Shoulberg
N
N
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004285:Dogs; D005260:Female; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D013268:Stimulation, Chemical; D013564:Sympathetic Nervous System / Q000502:physiology*; D014132:Trachea / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D010656:Phenylephrine; D003000:Clonidine; D009638:Norepinephrine