title: Cardiopulmonary responses to HCl infusion are mediated by thromboxane A2 but not by serotonin.
abstract: Intravenous infusion of HCl has been shown to elicit the release of thromboxane A2 (TxA2) which alters blood pressure and breathing independent of reductions in circulating blood pH. The present experiments were designed to determine if the release of serotonin (5-HT) in the anesthetized cat contributed to cardiorespiratory responses during acid infusion and, furthermore to define the source of TxA2, viz. blood or other tissues. To infuse HCl into the bloodstream without reducing circulating blood pH (= neutral acid-base infusion), an extracorporeal arteriovenous shunt (20 ml/min) between the femoral artery and femoral vein was installed. Into this loop, acid (0.25 M HCl), and approximately 10 cm downstream, base (0.25 M NaOH) could be infused whereby blood pH could be locally reduced in the blood within the loop. This procedure was performed in three groups of cats: one group which received no drugs, a second group that was pretreated with indomethacin (2.5 mg/kg) and a third group that received the 5-HT2 receptor antagonist, ketanserin (0.75 mg/kg), prior to the infusion. During neutral acid-base infusion in the nontreated animals, right ventricular blood pressure (PRV) increased and systemic arterial blood pressure (Pa) decreased. Respiratory frequency was increased, but total ventilation was not elevated because of a concomitant fall in tidal volume (VT). The response was transient and could not be evoked with repetitive infusions of HCl and NaOH. These responses were significantly attenuated in the indomethacin-treated animals, but persisted in the cats pretreated with ketanserin. In addition, TxB2, the stable degradation metabolite of TxA2, was elevated during the acid/base infusion, but there were no measurable changes in plasma 5-HT concentration. The source of TxA2 was likely to be the blood since TxB2 was increased in plasma when acid and base were added to blood in vitro. We conclude from these experiments that transient cardiorespiratory responses to HCl infusion are mediated by the release of TxA2 from the blood and do not involve serotonin.
authors.affiliation: Department of Physiology and Cell Biology, University of Kansas, Lawrence 66045.
authors.forename: J A
authors.initials: JA
authors.lastname: Orr
authors.forename: M
authors.initials: M
authors.lastname: Ernst
authors.forename: J
authors.initials: J
authors.lastname: Carrithers
authors.forename: H W
authors.initials: HW
authors.lastname: Shirer
mesh_terms: D000818:Animals; D002415:Cats; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007262:Infusions, Intravenous; D007650:Ketanserin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D012701:Serotonin / Q000097:blood / Q000502:physiology*; D013928:Thromboxane A2 / Q000097:blood / Q000502:physiology*
chemical_list: D012701:Serotonin; D013928:Thromboxane A2; D007650:Ketanserin; D006851:Hydrochloric Acid; D007213:Indomethacin