Calcium antagonist and the peripheral circulation: differences and similarities between PY 108–068, nicardipine, verapamil and diltiazem

Abstract

1 The effects of two dihydropyridines, PY 108–068 (PY) and nicardipine (N), and two other calcium antagonists, verapamil (V) and diltiazem (D), on regional blood flow were measured in open-chest cats, anaesthetized with chloralose-urethane. 2 Each substance was infused at 3 different dose rates, each for 10 min. The total doses given were 5 plus 10 plus 35 (total of 50) μg/kg for PY, 10 plus 20 plus 70 (total of 100) μg/kg for N and 100 plus 200 plus 700 (total of 1000) μg/kg for V and D. 3 All substances lowered blood pressure and increased total peripheral conductance. Heart rate was lowered only by V, D and PY. Cardiac output was markedly increased only by the diyhydroypridine derivatives; D had small and V almost no effects. 4 All substances increased coronary flow and redistributed it in favour of the subepicardial layer. All substances also increased blood flow to the brain. The effects of verapamil were comparatively small. 5 Skeletal muscle flow was increased strongly by the two dihydropyridine derivatives. D and V had negligible effects. 6 Blood flow to stomach and small intestine was only slightly increased. Flow to the kidneys increased slightly in diltiazem-treated animals but did not change with all other treatments. Flow to the liver, the adrenals, and the spleen remained unchanged or showed a tendency to decrease. 7 The organ conductances which reflect the active changes in vascular tone better than blood flow values, showed that there was a tendency towards vasodilatation even in most organs where blood flow tended to decrease. 8 Results obtained in an earlier series of experiments with nifedipine were very similar to those described here for N, except that nifedipine was about twice as potent. 9 Calcium antagonists were thus neither general peripheral vasodilators nor did they show a uniform pattern of preferential sites of action. The most important common features were increases in coronary and cerebral blood flow and the most important differences the divergent effects of the dihydropyridines on one side and V and D on the other side on skeletal muscle flow. The size of this vascular bed may help to explain why dihydropyridines appear to be particularly potent as peripheral vasodilators.