Effect of thromboxane A2 antagonist GR32191B on prostanoid and nonprostanoid receptors in the human internal mammary artery.

Arterial grafts have been demonstrated to be very effective for coronary artery bypass surgery. Thromboxane A2 (TXA2) is a potent vasoconstrictor for arterial grafts. To determine whether the specific TXA2 (TP) receptor antagonist GR32191B is effective in inhibition of prostanoid or nonprostanoid receptors, we studied the effect of GR32191B in human internal mammary artery (IMA) segments, taken from coronary bypass patients, in organ chambers. In IMA precontracted with U46619 (10 nM, n = 7), prostaglandin F2 alpha (PGF2 alpha 1 microM, n = 7), or potassium chloride (K+ 25 microM, n = 6). GR32191B induced 100.0 +/- 0, 97.86 +/- 2.14, or 45.87 +/- 7.63% relaxation. In other experiments, one IMA ring taken from each patient was used as a control and others from the same patient were allocated to other groups treated with different concentrations of GR32191B [3-300 nM for U46619, 30 nM-3 microM for PGF2 alpha, 300 nM-100 microM for K+, 3 microM norepinephrine (NE), and 3 microM for 5-hydroxytryptamine (5-HT)] for 1 h before concentration-contraction curves to these vasoconstrictors (expressed as percentage of K(+)-induced contraction force) were established. Treatment with GR32191B (300 nM) significantly decreased the contraction induced by U46619 (from 306.4 +/- 22.1 to 61.9 +/- 24.9%, p < 0.01) and that induced by PGF2 alpha (from 208.2 +/- 13.5 to 1.4 +/- 1.4%, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)