Effects of thromboxane A2 on thoracic aorta of young and old rats: use of selective thromboxane receptor antagonists.
Thromboxane A2 (TXA2) is a bioactive metabolite of arachidonic acid which produces vascular smooth muscle contraction and blood platelet aggregation. The goal of this study is to establish whether there are age-dependent differences of vascular contractility to TXA2. Thoracic aorta of F-344 rats of age 4-6 months (young) and 22-23 months (old) were used as a model to examine responses to U46619 [(15S)-hydroxy-11 alpha, 9 alpha-(epoxymethano)prosta-5Z,13E-dienoic acid; a TXA2 agonist] alone or in the presence of prostanoid (SQ 29,548) or nonprostanoid (trimetoquinol, TMQ) endoperoxide/TXA2 receptor antagonists. Maximal contractile responses (84 and 89% relative to KCl) and EC50 values (23 and 55 nmol/l, respectively) to U46619 were the same in aortic strips of young and old animals. Experimentally determined pA2 and pKB values for SQ 29,548 and TMQ as antagonists of U46619-mediated contraction were unchanged in aorta of young (9.09 and 5.83, respectively) and old (9.41 and 6.10, respectively) rats. We conclude that the reactivity and population of TXA2 receptors in rat vascular smooth muscle are unaffected by the aging process.
Shams
G
G
Division of Pharmacology, College of Pharmacy, Ohio State University, Columbus.
Wallace
L J
LJ
Miller
D D
DD
Feller
D R
DR
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000375:Aging / Q000502:physiology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D017482:Receptors, Thromboxane; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014213:Tretoquinol / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C024531:1-(2',4',5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline; C045749:SQ 29548; D014213:Tretoquinol