AJP - Heart and Circulatory Physiology, Vol 247, Issue 5 775-H783, Copyright © 1984 by American Physiological Society
Nitrendipine: effects on vascular responses and myocardial binding
W. McBride, A. Mukherjee, Z. Haghani, E. Wheeler-Clark, J. Brady, T. Gandler, L. Bush, L. M. Buja and J. T. Willerson
We have further defined the binding characteristics of [3H]nitrendipine to
myocardial microsomal membranes of cats, dogs, rats, and rabbits and to
canine coronary vasculature (1.5-3.0 mm OD), and we have studied
nitrendipine's effect on contractile responses in isolated feline cardiac
muscle and canine coronary arteries. [3H]nitrendipine binding is rapid,
saturable, and reversible in all four species and in all of these tissues.
Feline myocardium has a single binding site with a dissociation constant
(KD) of 1.94 nM. Canine myocardium may have two classes of binding sites,
with the high-affinity site having a KD of 0.17 nM. Nitrendipine depresses
contractility in isolated feline cardiac muscle and canine coronary
arteries in a dose-dependent manner [half-maximal dose (ED50) 0.20 microM
in isolated feline cardiac muscle and 1.6-6.3 nM for potential dependent
contractile responses in isolated canine coronary arteries] and severely
blunts the contractile response to increases in extracellular calcium
concentration in isolated feline papillary muscles. In contrast to
verapamil and D 600, nitrendipine does not prevent the treppe phenomenon.
In isolated feline cardiac muscle and large canine coronary arteries, the
minimal nitrendipine concentration required for specific binding and for
depression of contractile responses is similar. However, only in large
canine coronary arteries is the ED50 for nifedipine's depression of
contractility similar to the KD for [3H]nitrendipine binding in the
respective tissue.
