Effects of diltiazem and its analogue siratiazem on contraction and 45Ca2+ uptake in sheep coronary artery rings.
1. Siratiazem, an analogue of diltiazem designed to be resistant to N-demethylation, was compared with diltiazem for inhibition of Ca(2+)-induced contraction of depolarized coronary artery rings from the sheep. There was no significant difference in potency between siratiazem and diltiazem in the presence of normal physiological salt solution (IC25 for siratiazem 0.13 +/- 0.04 microM and for diltiazem 0.08 +/- 0.02 microM) or one mimicking some of the conditions that occur during myocardial ischaemia (hypoxia, acidosis, reduced glucose and addition of lactate). 2. K(+)-stimulated 45Ca2+ uptake in coronary artery rings was also inhibited by siratiazem and diltiazem with similar potencies. 3. It is concluded that siratiazem inhibits Ca2+ entry in coronary vascular smooth muscle equipotently with diltiazem and that this effect is not modified by some of the changes that occur during myocardial ischaemia.
Hagerty
M
M
Department of Physiology and Pharmacology, Strathclyde Institute for Drug Research, University of Strathclyde, Glasgow, Scotland.
Panesar
M
M
Wadsworth
R
R
Kane
K
K
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D004110:Diltiazem / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D012756:Sheep
D000889:Anti-Arrhythmia Agents; D011189:Potassium Chloride; C085176:siratiazem; D004110:Diltiazem; D002118:Calcium