Potentiation of vagal contractile response by thromboxane mimetic U-46619.
We studied the effect of the thromboxane mimetic U-46619 on tracheal smooth muscle contraction caused by bilateral stimulation of the vagus nerves in 14 mongrel dogs in situ. The parasympathetic contractile response was studied isometrically after beta-adrenergic blockade with 2 mg/kg iv propranolol plus 20 micrograms X kg-1 X min-1 continuous intravenous infusion and blockade of endogenous prostaglandin synthesis with 5 mg/kg iv indomethacin. An initial frequency-response curve was generated by electrical stimulation of the caudal ends of cut cervical vagi over the range of frequencies 2-25 Hz (constant 25 V) at 15-s intervals. In five dogs, 10(-10) to 10(-8) mol of the thromboxane mimetic (15S)-hydroxyl-11 alpha,9 alpha-(epoxymethano)prosta-5Z,13E-dienoic acid (U-46619) was injected selectively into the tracheal arterial circulation, causing a transient contractile response (less than or equal to 10 g/cm). Additional frequency response studies were generated 7 min before and 1, 15, 30, 45, and 60 min after U-46619. Substantial augmentation of tracheal contraction to efferent vagal stimulation was observed after U-46619 for all frequencies greater than 4 Hz (P less than 0.02). Augmentation of vagally mediated contraction was not observed in four other dogs after equivalent tracheal contraction was elicited without U-46619. Similarly, in four separate dogs, augmentation of tracheal contraction was not observed when acetylcholine was given instead of vagal stimulation after U-46619. We conclude that the thromboxane analogue, U-46619, causes augmentation of tracheal contractile response induced by efferent vagus nerve stimulation. Potentiation is caused by a prejunctional action of U-46619 and is not induced by nonspecific precontraction with another agonist.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D013931:Thromboxanes / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology*
D011450:Prostaglandin Endoperoxides, Synthetic; D013931:Thromboxanes; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine