As presented by Dembowsky et al. and Rounding et al. at the 1994 AHA meeting, Bay y 5959 is a positive dihydropyridine inotrope that selectively promotes Ca2+ entry into myocardial cells, probably by a direct, Ca2+ channel mechanism, minimizing the increase in O2 consumption compared to catecholamines or phosphodiesterase inhibitors. The Ca2+ promoting effect was selective for cardiac as opposed to vascular muscle cells, and was protective against stunning by 10 min occlusion of the left anterior descending coronary artery. Vascular muscle cells are widely believed to be more sensitive to known dihydropyridine Ca2+ agonists, e.g., Bay k 8644, than are cardiac muscle cells. Several explanations for vascular muscle selectivity have been postulated, including the relatively depolarized resting membrane potentials, increased affinity, and additional Ca2+ channel antagonist binding sites. While the puzzle of vascular selectivity of dihydropyridines is far from being solved, selectivity for cardiac muscle is an interesting problem that may help to reveal mechanistic factors. This project began in September, 1995, and reflects only initial planning stages.
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