DIFFERENTIAL-EFFECTS OF THE CALCIUM-ANTAGONIST MIBEFRADIL IN EPICARDIAL AND INTRAMYOCARDIAL CORONARY-ARTERIES

The efficacy of vasodilation depends on the drug and the contractile a gonist involved. Furthermore, vasodilation also may be detrimental (i. e., coronary steal), possibly depending on the anatomic site and/or ac tion of the vasodilator. We investigated the effects of Ca2+ antagonis m in porcine epicardial and intramyocardial coronary arteries suspende d in organ chambers filled with physiological salt solution (95% O-2/5 % CO2, 37 degrees C); isometric tension was measured. In epicardial ve ssels contracted with KCl, the thromboxane analogue U 46619, or endoth elin-1 (ET-1), relaxations to the Ca2+ antagonist mibefradil were most effective after precontraction with KCl, followed by U 46619 and ET-1 . In intramyocardial vessels, the contraction to KCl, U 46619, and par ticularly ET-1, was much more effectively inhibited by mibefradil than in epicardial arteries. In vessels preincubated with mibefradil, the drug was moderately effective in preventing the initiation of contract ions. Preincubation with the inhibitor of nitric oxide production (NO) , L(omega)-nitro arginine methyl ester (L-NAME) or endothelium removal , did not increase relaxations to mibefradil. However, epicardial but not intramyocardial vessels incubated with mibefradil exhibited enhanc ed relaxations to bradykinin (BK) and sodium nitroprusside (SNP) as co mpared with control. Thus, Ca2+ antagonism is particularly effective i n intramyocardial coronary arteries. In addition to its inhibitory eff ects on contractility, calcium antagonism facilitates the effects of e ndothelium-derived NO in epicardial coronaries at the level of vascula r smooth muscle (VSM).