Coronary vasodilator and cardiac effects of NKY-722, a novel hydrophilic 1,4-dihydropyridine derivative, in the blood-perfused dog heart.
The coronary vasodilator and cardiac effects of NKY-722, a novel hydrophilic 1,4-dihydropyridine derivative, were evaluated in isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node, and papillary muscle preparations of dogs. NKY-722 was administered intraarterially. NKY-722 increased coronary blood flow in all preparations. In SA node preparations, NKY-722 reduced sinus rate and produced atrial standstill in large doses. The dose that produced a 15% (nearly half-maximum) decrease in sinus rate was about six times the dose that doubled coronary blood flow. In AV node preparations, NKY-722 prolonged AV conduction time and produced second- or third-degree AV block in large doses only when administered into the artery supplying the AV node. The dose that produced a 15% (nearly half-maximum) increase in AV conduction time was about 3.5 times the dose that doubled coronary blood flow. In paced papillary muscle preparations, NKY-722 reduced the force of contraction. However, the dose that produced a 50% decrease in the force of contraction of the paced papillary muscle was about 100 times the dose that doubled coronary blood flow. In spontaneously beating papillary muscle preparations, NKY-722 failed to change the beating rate. The vasodilator effect of NKY-722 was of longer duration than the negative chronotropic, dromotropic, and inotropic effects. These results indicate that NKY-722 is highly vasoselective, and the cardiovascular profile of NKY-722 is essentially identical to that of currently available, lipophilic 1,4-dihydropyridine calcium antagonists.
Imagawa
J
J
Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Satoh
K
K
Taira
N
N
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001283:Atrioventricular Node / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D010477:Perfusion; D012849:Sinoatrial Node / Q000187:drug effects; D014665:Vasodilator Agents
D000959:Antihypertensive Agents; D004095:Dihydropyridines; D014665:Vasodilator Agents; C058351:NKY 722