Effects of potassium channel opener KRN4884 on human conduit arteries usedas coronary bypass grafts

Aims The effects of a new potassium channel opener KRN4884 on human arterie s have not been studied. This study was designed to investigate the effects of KRN4884 on the human internal mammary artery (IMA) in order to provide information on possible clinical applications of KRN4884, for preventing an d relieving vasospasm of arterial grafts in coronary artery bypass grafting . Methods IMA segments (n=140) taken front patients undergoing coronary surge ry were studied in the organ chamber. Concentration-relaxation curves for K RN4884 were established in the IMA precontracted with noradrenaline (NA), 5 -hydroxytryptamine (5-HT), angiotensin II (ANG II), and endothelin-1 (ET-1) . The effect of glibenclamide (GBC) on the KRN4884-induced relaxation was a lso examined in NA or 5-HT-precontracted IMA. Concentration-contraction cur ves for the four vasoconstrictors were constructed without/with pretreatmen t of KNR4884 (1 or 30 mu M) for 15 min. Results KRN4884 induced less relaxation (P<0.05) in the precontraction indu ced by ET-1 (72.9+/-5.5%) than by ANG II (94.2+/-3.2%) or NA (93.7+/-4.1%) with lower EC50 (P< 0.05) for ANG II (- 8.54+/-0.54 log M) than that for NA (- 6.14+/-0.15 log M) or ET-1 (- 6.6+/-0.34 log M). The relaxation in the IMA pretreated with GBC was less than that in control (P<0.05). KRN4884-pre treatment significantly reduced the contraction (P<0.05) induced by NA (151 .3+/-18.4% vs 82.7+/-8.7%), 5-HT (82.7+/-12.2% vs 30.1+/-7.3%), and ANG II (24.3+/-6.3% vs 5.4+/-1.6%), but did not significantly reduce the contracti on induced by ET-1 (P>0.05). Conclusion KRN4884 has marked vasorelaxant effects on the human IMA contrac ted by a variety of vasoconstrictors and the effect is vasoconstrictor-sele ctive.