Transmural gradient of coronary blood flow following dihydropyridine calcium antagonists and other vasodilator drugs.

The effects of the dihydropyridine calcium antagonists, nifedipine, nitrendipine and FR 7534 on the transmural distribution of coronary blood flow (endo/epi) were compared to the structurally unrelated calcium antagonists, verapamil and diltiazem and to the non-calcium antagonist vasodilator drugs, chromonar and dipyridamole in anesthetized dogs. The increase in transmural blood flow produced by diltiazem, verapamil, chromonar and dipyridamole was equally distributed between subendocardium and subepicardium (no change in endo/epi). On the other hand, the increase in myocardial blood flow produced by the dihydropyridine calcium antagonists nifedipine, nitrendipine and FR 7534 was relatively selective for subepicardial regions resulting in a significant and dose-related decrease in endo/epi. This unusual effect of the dihydropyridine calcium antagonists to produce a redistribution of flow within normal myocardium was not shared by the non-dihydropyridine calcium antagonists or non-calcium antagonist vasodilators studied. The redistribution of flow was not related to changes in heart rate, aortic blood pressure or to the level of total coronary blood flow. Such an effect may be related to the distribution of dihydropyridine receptors across the left ventricular wall, antagonism of the action of adenosine, or changes in regional intramyocardial tissue pressure and extravascular resistance.