Vasorelaxant properties of nicorandil on human radial artery.

Abstract

The radial artery is becoming popular as a conduit for coronary artery surgery but there is concern about its tendency to vasospasm. Diltiazem is used clinically in an effort to prevent vasospasm but there are suggestions that it is relatively ineffective. The first aim of the study was to test the effectiveness of Ca(2+) antagonists against vasospasm evoked by vasoconstrictor agonists. Because a large component of vasospasm was resistant to Ca(2+) antagonists, the second aim was to test if a different class of vasodilator, nicorandil, might relax the residual tone. Isometric tension was recorded in human radial artery segments harvested from patients undergoing myocardial revascularization surgery. Diltiazem at 10 microM, which strongly inhibits L-type voltage-gated Ca(2+) channels, induced partial relaxation (mean+/-SEM, 44.6+/-3.5%, n=31) of phenylephrine-evoked contraction, but only 14.0+/-4.1% (n=10) and 12. 2+/-4.2% (n=10) relaxation of U46619- (a thromboxane A(2) analogue) or endothelin-1-evoked contraction. Strikingly, nicorandil relaxed agonist-evoked contractions that were resistant to diltiazem or nicardipine. In the absence of a Ca(2+) antagonist, nicorandil (30 microM) evoked 74.1+/-5.6% (n=24), 36.8+/-9.3% (n=10) and 64.5+/-7. 9% (n=14) relaxation of phenylephrine-, U46619- and endothelin-1-evoked contractions. Nicorandil has a marked relaxant effect on contractions evoked by three different vasoconstrictor agonists, and relaxes vasospasm that is resistant to conventional Ca(2+) antagonists. These in vitro data suggest that nicorandil might be a useful drug for the inhibition of radial artery vasospasm in myocardial revascularization surgery.