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Effects of potassium channel opener KRN4884 on human conduit arteries used as coronary bypass grafts
Author(s) -
Ren Zhen,
Floten Storm,
Furnary Anthony,
Liu Minghui,
Gately Hugh,
Swanson Jeffrey,
Ahmad Aftab,
Yim Anthony P. C.,
He GuoWei
Publication year - 2000
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2000.00235.x
Subject(s) - glibenclamide , contraction (grammar) , artery , coronary arteries , medicine , bypass grafting , angiotensin ii , coronary artery bypass surgery , endothelin 1 , potassium channel opener , potassium , anesthesia , cardiology , chemistry , potassium channel , endocrinology , blood pressure , receptor , diabetes mellitus , organic chemistry
AimsThe effects of a new potassium channel opener KRN4884 on human arteries 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 and relieving vasospasm of arterial grafts in coronary artery bypass grafting.MethodsIMA segments ( n = 140) taken from patients undergoing coronary surgery were studied in the organ chamber. Concentration‐relaxation curves for KRN4884 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 also examined in NA or 5‐HT‐precontracted IMA. Concentration‐contraction curves for the four vasoconstrictors were constructed without/with pretreatment of KNR4884 (1 or 30 µ m ) for 15 min.ResultsKRN4884 induced less relaxation ( P < 0.05) in the precontraction induced by ET‐1 (72.9 ± 5.5%) than by ANG II (94.2 ± 3.2%) or NA (93.7 ± 4.1%) with lower E C 50 ( 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 (−6.69 ± 0.34 log m ). The relaxation in the IMA pretreated with GBC was less than that in control ( P < 0.05). KRN4884‐pretreatment 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 contraction induced by ET‐1 ( P > 0.05).ConclusionKRN4884 has marked vasorelaxant effects on the human IMA contracted by a variety of vasoconstrictors and the effect is vasoconstrictor‐selective.