Inhibition of vasoconstriction by the thromboxane A2 antagonist GR32191B in the human radial artery.
OBJECTIVE
The newly revived coronary bypass graft, the radial artery (RA), is more spastic than the internal mammary artery. Thromboxane A2 is a potent vasoconstrictor for arterial grafts. This study was therefore designed to determine whether the specific thromboxane A2 (TP) receptor antagonist, GR32191B, is effective in inhibition of prostanoid or nonprostanoid receptors in the RA.


METHODS
The effect of GR32191B was studied in human RA segments, taken from coronary bypass patients, in organ chambers. Two effects of GR32191B were tested: (1) the relaxation induced by GR32191B in the RA precontracted with the TP receptor agonists U46619 and PGF2alpha or nonprostanoid vasoconstrictors (noradrenaline [NA], angiotensin II [AII], and K+ ) and (2) the inhibitory effect of GR32191B on TP receptor agonists and nonprostanoid vasoconstrictors.


RESULTS
In U46619 (10 nm, n=7) and PGF2alpha (1 microm, n=7) precontracted RA, GR32191B induced 100% relaxation (10-100 microm ) but not after precontraction with nonprostanoid stimuli (5.8% for K+, 25 mm, n=6, 24.4% for NA, 3 microm, n=8, and 53.2% for AII, 3 nm, n=5) (P<0.001). Treatment with GR32191B (30 nm ) significantly depressed the contraction with U46619 (from 160.1+/-11.0% to 116.8+/-13.1%, P<0. 05) or PGF2alpha (from 91.3+/-12.3% to 42.2+/-9.2%, P<0.01). The contraction was further abolished by 3 microm GR32191B. However, GR32191B at 3 microm did not significantly inhibit the contraction induced by either NA, AII, or K+.


CONCLUSIONS
GR32191B is a highly potent and specific TP receptor antagonist for the human RA. It may be particularly useful in inhibiting TXA2-mediated vasoconstriction and therefore in reducing the complications related to vasospasm in this graft.
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Cardiovascular Research Laboratory and Division of Cardiothoracic Surgery, Grantham Hospital, Department of Surgery and the Institute of Cardiovascular Science and Medicine, University of Hong Kong, Hong Kong.
Yang
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CQ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001026:Coronary Artery Bypass; D015237:Dinoprost / Q000494:pharmacology; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011188:Potassium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D017534:Radial Artery / Q000187:drug effects*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D001713:Biphenyl Compounds; D006538:Heptanoic Acids; D011448:Prostaglandin Antagonists; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost; C060013:vapiprost; D011188:Potassium; D009638:Norepinephrine