Thromboxane A2/endoperoxide receptors mediate cholinergic constriction of rabbit lung microvessels.
Using an X-ray television system, we directly measured the internal diameter (ID; 100-1,000 microns) of small pulmonary arteries and analyzed the effects of cyclooxygenase inhibition and thromboxane A2/prostaglandin endoperoxide (TP) receptor blockade on the ID reductions in response to vagal nerve stimulation (VNS; 16 Hz) and injection of acetylcholine (ACh; 0.3 micrograms) in anesthetized rabbits. The ID reductions of the small arteries in response to VNS and ACh were completely abolished by pretreatment with cyclooxygenase inhibitors indomethacin and meclofenamate. Those reductions were also eliminated by pretreatment with TP receptor antagonists AA-2414 and Ono 3708. Both TP receptor antagonists abolished the ID reduction to thromboxane A2 mimetic U-46619 but did not affect the reduction to norepinephrine. The ID reductions in response to VNS and ACh were eliminated by atropine. The reduction in response to VNS was abolished by hexamethonium bromide, whereas the reduction in response to ACh was not altered by hexamethonium bromide. The results indicate that vasoconstrictions of the rabbit small pulmonary arteries in response to VNS and exogenous ACh are mediated by TP receptors as well as muscarinic receptors. The data suggest that during VNS endogenous ACh acts on muscarinic receptors to constrict the small arteries mainly by generating thromboxane A2 or prostaglandin endoperoxide.
Shirai
M
M
Department of Cardiac Physiology, National Cardiovascular Center Research Institute, Osaka, Japan.
Ninomiya
I
I
Sada
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016227:Benzoquinones; D001794:Blood Pressure / Q000187:drug effects; D002799:Cholinergic Fibers / Q000502:physiology; D004558:Electric Stimulation; D006538:Heptanoic Acids; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000098:blood supply*; D008833:Microcirculation / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D011809:Quinones / Q000494:pharmacology; D011817:Rabbits; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000502:physiology*; D017482:Receptors, Thromboxane; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D013931:Thromboxanes / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D016227:Benzoquinones; D006538:Heptanoic Acids; D011809:Quinones; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013931:Thromboxanes; C060230:seratrodast; D013928:Thromboxane A2; C049855:ONO 3708; D000109:Acetylcholine; D007213:Indomethacin