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

Citation
Z. Ren et al., Effects of potassium channel opener KRN4884 on human conduit arteries usedas coronary bypass grafts, BR J CL PH, 50(2), 2000, pp. 154-160
Citations number
41
Categorie Soggetti
Pharmacology,"Pharmacology & Toxicology
Journal title
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
ISSN journal
03065251 → ACNP
Volume
50
Issue
2
Year of publication
2000
Pages
154 - 160
Database
ISI
SICI code
0306-5251(200008)50:2<154:EOPCOK>2.0.ZU;2-7
Abstract
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.