The intervessel selectivity indexes of the calcium entry blockers amlodipine, felodipine, isradipine, nicardipine, nifedipine, nitrendipine, diltiazem and verapamil were assessed by determining the potency of these compounds [concentration decreasing tension developed by KCl in blood vessels by 50% (bvlC50)] to relax several KCl-precontracted blood vessels (femoral, jugular and saphenous veins and left anterior descending and left circumflex coronary and renal arteries) precontracted with KCl. The concentrations of KCl (25 mM for arteries and 50 mM for veins) used gave a similar response in these vessels. Intervessel selectivity indexes are the ratios of the bvlC50 determined in two different vessels. The negative inotropic potency (hlC50) was ascertained in paced (2 Hz), isoproterenol-(10 nM) supported atrial strips, and for three of the compounds, in papillary muscles. This allowed calculation of heart/vessel selectivity or vasoselectivity (ratio of hlC50 and bvlC50). All compounds overcame almost entirely (85-100%) the vessel contractile response to KCl and strongly reduced (65-90%) the tension developed by myocardial preparations. The rank order for vasorelaxant potency (bvlC50 from approximately 1 to approximately 700 nM) was generally as follows: isradipine > or = nifedipine > or = nitrendipine > or = amlodipine > or = verapamil > or = felodipine > or = nicardipine > or = diltiazem. However, the rank order for negative inotropic potency (hlC50 spanning from approximately 200 to approximately 6000 nM) was isradipine > or = nifedipine > or = verapamil > or = diltiazem > or = amlodipine > or = nitrendipine > or = felodipine > or = nicardipine. All compounds were generally more potent in relaxing capacitance than conductance vessels. Furthermore, of the capacitance vessels, the jugular vein was the least susceptible to relaxation; among the conductance vessels, five of the eight compounds relaxed renal arteries with greater potency than coronary arteries. Consequently, the value of the heart/vessel selectivity index is intrinsically dependent on the vessel used to calculate it. Overall, nitrendipine was the most vasoselective calcium entry blocker studied, with selectivity indexes ranging from 28 to 523. In conclusion, 1,4-dihydropyridine calcium entry blockers generally have a much greater affinity for calcium channels present in micropig veins than in heart muscle myocytes. This is possibly due to tissue-specific features of L-type calcium channels. Finally, comparing the vasoselectivity index of various compounds has validity only if this index is calculated by using the same experimental procedure applied to the same vascular tissue and the same heart preparation taken from the same species.