title: Thromboxane mediation of the pressor response to infused angiotensin II.
abstract: The role of thromboxane A2(Tx) in mediating the pressor response to angiotensin II (AII) was studied in anesthetized rats. Intravenous AII (500 ng/kg/min) increased mean arterial pressure (MAP) by 35 +/- 3 mm Hg and increased the excretion of prostaglandin PGE2, the metabolites of prostacyclin (6kPGF1 alpha) and Tx (TxB2) (P less than .05). A similar pressor infusion of the alpha 1-adrenoreceptor agonist phenylephrine (PE) increased the excretion of PGE2 and 6kPGF1 alpha but not TxB2. The increases in MAP and prostaglandin excretion produced by AII were reversed by the AII-receptor antagonist saralasin (10 micrograms/kg/min) while those produced by PE were reversed by the alpha-adrenoreceptor antagonist phenoxybenzamine (250 micrograms/kg). The Tx receptor antagonist, SQ-29,548 (8 mg/kg) attenuated (P less than .0001) the AII-induced rise in MAP (13 +/- 1 mm Hg) but did not modify the pressor response to PE. The Tx synthetase inhibitor, UK-38,485 (50 mg/kg/d) given for 3 days, reduced basal TxB2 excretion by 75% and also attenuated (P less than .001) the AII-induced rise in MAP (11 +/- 2 mm Hg). However, when given 40 min before the AII infusion, UK-38,485 did not attenuate the pressor response. In separate groups of rats, the log dose-response curve for bolus intravenous injection of AII was shifted to the right by SQ-29,548 while that for PE was unaffected.
  
  
  CONCLUSIONS
  1) AII releases Tx; 2) Tx release is not secondary to hypertension; and 3) Tx can mediate up to two-thirds of the short-term pressor response to high-dose AII infusion.
authors.affiliation: Department of Medicine, University of Florida College of Medicine, Gainesville.
authors.forename: C S
authors.initials: CS
authors.lastname: Wilcox
authors.forename: W J
authors.initials: WJ
authors.lastname: Welch
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology* / Q000652:urine; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015232:Dinoprostone / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007262:Infusions, Intravenous; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology; D010656:Phenylephrine / Q000652:urine; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012504:Saralasin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013931:Thromboxanes / Q000502:physiology*; D014556:Urine
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D007093:Imidazoles; D013931:Thromboxanes; D010643:Phenoxybenzamine; D000804:Angiotensin II; D010656:Phenylephrine; C039242:dazmegrel; D013928:Thromboxane A2; C045749:SQ 29548; D013930:Thromboxane-A Synthase; D012504:Saralasin; D015232:Dinoprostone