Coronary vasodilator and cardiac effects of NKY-722, a novel hydrophilic 1,4-dihydropyridine derivative, in the blood-perfused dog heart.

Abstract

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.

• Authors: J Imagawa, K Satoh, N Taira
• Journal: Cardiovascular drugs and therapy (Cardiovasc Drugs Ther) Vol. 3 Issue 1 Pg. 81-90 (Mar 1989) ISSN: 0920-3206 [Print] United States
• PMID: 2487526 (Publication Type: Journal Article)

Chemical References

• Antihypertensive Agents
• Dihydropyridines
• Vasodilator Agents
• NKY 722

Topics

• Animals
• Antihypertensive Agents (pharmacology)
• Atrioventricular Node (drug effects)
• Cardiac Pacing, Artificial
• Coronary Circulation (drug effects)
• Coronary Vessels (drug effects)
• Dihydropyridines (pharmacology)
• Dogs
• Female
• Heart (drug effects)
• Heart Rate (drug effects)
• In Vitro Techniques
• Male
• Myocardial Contraction (drug effects)
• Papillary Muscles (drug effects)
• Perfusion
• Sinoatrial Node (drug effects)
• Vasodilator Agents