RT Journal Article
SR Electronic
T1 Vasodilator Action of Calcium Antagonists in Coronary Arteries<em>In Vitro</em>
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 634
OP 642
VO 281
IS 2
A1 Stanley Kalsner
YR 1997
UL http://jpet.aspetjournals.org/content/281/2/634.abstract
AB Calcium antagonists have routinely been assumed to inhibit the contractions of arterial smooth muscle through block of membrane channels. The effects of nifedipine and diltiazem on contractions were examined in in vitro preparations of cattle coronary artery, one of the key therapeutic targets of calcium antagonists, to determine if alternate mechanisms of action are involved. Contractions elicited in calcium-free Krebs, in the presence of U 46619, to potassium channel inhibitors (4-aminopyridine and tetraethylammonium) and to a Na+-K+-ATPase inhibitor (ouabain), were antagonized by low concentrations of nifedipine (3 × 10− 9 - 3 × 10− 8M) and by diltiazem (3 × 10− 8 and 1 × 10− 7 M). Contractions produced in calcium-free Krebs to KCl (50 mM) were antagonized similarly by calcium antagonists. Contractions to depolarizing agents in calcium-free Krebs were antagonized at lower concentrations of nifedipine than comparably elicited responses in Krebs containing 2.3 mM calcium. In addition, higher concentrations of nifedipine were required to antagonize contractions to extracellular calcium, produced in preparations maintained in calcium-free Krebs in the presence of KCl (50 mM), than were needed to block contractions to KCl or to potassium channel inhibitors elicited in calcium-free Krebs. Pretreatment of preparations in calcium-free Krebs with ryanodine (30 μM) did not reduce the nifedipine-sensitive contractions elicited in calcium-free Krebs. It is concluded that at least some of the therapeutic effects of calcium antagonists on arterial tone may be the consequence of antagonism at vascular smooth muscle cell site(s) at which calcium is released or interacts, rather than of block of calcium entry through membrane L channels. The American Society for Pharmacology and Experimental Therapeutics