title: C3a57-77, a C-terminal peptide, causes thromboxane-dependent pulmonary vascular constriction in isolated perfused rat lungs.
abstract: Pulmonary hypertension occurs after the intravascular activation of complement. However, it is unclear which activated complement fragments are responsible for the pulmonary vascular constriction. We investigated the 21-carboxy-terminal peptide of C3a (C3a57-77) to see if it would cause pulmonary vascular constriction when infused into isolated buffer-perfused rat lungs. Injection of C3a57-77 (225 to 450 micrograms) caused mean pulmonary arterial pressure (Ppa) to rapidly increase. However, the response was transient, with Ppa returning to baseline within 10 min of its administration. C3a57-77 also resulted in an increase in lung effluent thromboxane B2 (TXB2), concomitant with the peak increase in Ppa. C3a57-77 did not affect the amount of 6-keto-PGF1 alpha in the same effluent samples. Indomethacin inhibited the C3a57-77-induced pulmonary artery pressor response and the associated TXB2 production. Indomethacin also decreased lung effluent 6-keto-PGF1 alpha. The thromboxane synthetase inhibitors CGS 13080 and U63,357 inhibited the C3a57-77-induced pulmonary artery pressor response and TXB2 production without affecting 6-keto-PGF1 alpha. These inhibitors did not inhibit pulmonary artery pressor responses to angiotensin II. Tachyphylaxis to C3a57-77 occurred because a second dose of C3a57-77 administered to the same lung failed to cause a pulmonary artery pressor response or TXB2 production. The loss of the pressor response was not due to a C3a57-77-induced decrease in pulmonary vascular responsiveness because pressor responses elicited by angiotensin II were not altered by lung contact with C3a57-77. Thus, C3a57-77 caused thromboxane-dependent pulmonary vascular constriction in isolated buffer perfused rat lungs.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0360.
authors.forename: M L
authors.initials: ML
authors.lastname: Morganroth
authors.forename: S O
authors.initials: SO
authors.lastname: Schoeneich
authors.forename: G O
authors.initials: GO
authors.lastname: Till
authors.forename: P A
authors.initials: PA
authors.lastname: Ward
authors.forename: S J
authors.initials: SJ
authors.lastname: Horvath
authors.forename: M M
authors.initials: MM
authors.lastname: Glovsky
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis / Q000096:biosynthesis; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015926:Complement C3a / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010477:Perfusion / Q000379:methods; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D013929:Thromboxane B2 / Q000032:analysis / Q000096:biosynthesis*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
chemical_list: D001572:Benzofurans; D016861:Cyclooxygenase Inhibitors; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; C062930:complement C3a, (57-77); D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015926:Complement C3a; C037787:pirmagrel; D013930:Thromboxane-A Synthase; C039936:furegrelate; D007213:Indomethacin