Thromboxane receptor agonists enhance adrenergic neurotransmission in rabbit isolated mesenteric arteries.
Two thromboxane receptor agonists, carbocyclic thromboxane A2 (CTA) and 9,11-dideoxy-11,9-epoxymethano prostaglandin F2 alpha (U46619), were examined for their influence on basal force and electrically induced force of isolated superior mesenteric arterial rings from rabbits. Both CTA and U46619 contracted the arterial rings and augmented contractile responses to electrical stimulation (4-20 Hz). The CTA and U46619 also augmented contractile responses to norepinephrine (P less than .05) and enhanced norepinephrine release in response to a 16 Hz electrical stimulation (P less than .05). The increases in basal force, neurogenic responses and norepinephrine release were prevented by the thromboxane receptor antagonist, (1S-[1-alpha,2-beta(5Z),3-beta, 4-alpha])-7-[3- [(2- [(phenylamino)carbonyl]hydrazino]methyl]-7- oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid. The U46619 was more potent than CTA and had a more consistent effect on norepinephrine release. These results are consistent with the hypothesis that thromboxane receptor agonists augment adrenergic neurogenic responses via thromboxane receptors. The mechanism of the enhanced neurogenic responses involved both pre- and postjunctional effects of the thromboxane receptor agonists.
Trachte
G J
GJ
Department of Pharmacology, University of Minnesota-Duluth, School of Medicine.
Stein
E A
EA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D011817:Rabbits; D011982:Receptors, Prostaglandin / Q000187:drug effects*; D017482:Receptors, Thromboxane; D009435:Synaptic Transmission / Q000187:drug effects; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D013931:Thromboxanes / Q000096:biosynthesis; D014661:Vasoconstriction / Q000187:drug effects
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013931:Thromboxanes; C024587:thromboxane A2, carbocyclic; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D009638:Norepinephrine