Phasic contractions of canine and human coronary arteries induced by potassium channel blockers.
To gain insight into mechanisms underlying phasic coronary vasospasm in patients with variant angina pectoris, we studied whether phasic contractions could be induced in isolated canine and human coronary arteries by agents which block potassium channels. Phasic contractions of canine coronary arteries were always induced by 3,4-diaminopyridine (10(-2) M) and less frequently by 4-aminopyridine (10(-2) M). These agents also caused phasic contractions in human, swine and monkey coronary arteries and in canine basilar, carotid, renal and femoral arteries. The cycle length of phasic coronary contractions ranged from 30 sec to 1 hour, and the developed tension was 2.5 times greater than for potassium contractions. The contractions continued for more than 11 hours. Morphologically, perinuclear vacuolization, a characteristic change of vasospasm, appeared in the coronary smooth muscles. The phasic contractions were not eliminated by tetrodotoxin, atropine, phentolamine or yohimbine, but they were eliminated by nicorandil which activates potassium channels and nifedipine which blocks slow calcium channels. The results indicate that potassium channel blockers can induce phasic arterial contractions.
D015761:4-Aminopyridine; D000328:Adult; D000368:Aged; D000077770:Amifampridine; D000631:Aminopyridines / Q000494:pharmacology; D000788:Angina Pectoris, Variant / Q000503:physiopathology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000648:ultrastructure; D003329:Coronary Vasospasm / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects* / Q000648:ultrastructure; D004285:Dogs; D005260:Female; D006801:Humans; D007473:Ion Channels / Q000187:drug effects*; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D020108:Nicorandil; D009543:Nifedipine / Q000494:pharmacology; D013552:Swine; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D000631:Aminopyridines; D007473:Ion Channels; D013757:Tetraethylammonium Compounds; D009536:Niacinamide; D020108:Nicorandil; D015761:4-Aminopyridine; D009543:Nifedipine; D000077770:Amifampridine