Thromboxane mediation of the pressor response to infused angiotensin II.
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.
Wilcox
C S
CS
Department of Medicine, University of Florida College of Medicine, Gainesville.
Welch
W J
WJ
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
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