A group of racemic 4-aryl(heteroary)-1,4-dihydro-2,6-dimethyl-3-nitropyridine-5-carboxylates possessing a potential nitric oxide donor C-5 O 2 -alkyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate ester [alkyl ¼ (CH 2 ) n , n¼ 1-4] substituent were synthesized using a modified Hantzsch reaction. Compounds having a C-4 2-trifluoromethylphenyl ( ), 2-pyridyl (17), or benzofurazan-4-yl (20) substituent generally exhibited more potent smooth-muscle calcium channel antagonist activity (IC 50 values in the 0.55 to 38.6 mM range) than related analogs having a C-4 3-pyridyl (18), or 4-pyridyl ( ) substituent with IC 50 values 4 29.91 mM, relative to the reference drug nifedipine (IC 50 ¼ 0.0143 mM). The point of attachment of C-4 isomeric pyridyl substituents was a determinant of antagonist activity where the relative potency profile was 2-pyridyl 4 3-pyridyl and 4-pyridyl. Subgroups of compounds 16a-d, 17a-d, and 20a-d having alkyl spacer groups of variable chain length [-CO 2 (CH 2 ) n O-, n ¼ 1-4] exhibited small differences in calcium channel antagonist potency. Replacement of the ester ''methyl'' moiety of Bay K 8644 by an O 2 -alkyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate group provided the Bay K 8644 group of analogs 16a-d that retained the desired cardiac positive inotropic effect. The most potent compound in this group, O 2 -ethyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate (16b, EC 50 ¼ 0.096 mM) is about eightfold more potent positive inotrope (cardiac calcium channel agonist) than the reference compound Bay K 8644 (EC 50 ¼ 0.77 mM). A similar replacement of the ester ''isopropyl'' group in the C-4 benzofurazan-4-yl group of compounds by an O 2 -alkyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate ester substituent provided compounds 20 (n ¼ 1 and 4) that were approximately equipotent cardiac positive inotropes with the parent reference compound PN 202-791 (3, EC 50 ¼ 9.40 mM). The O 2 -alkyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2diolate ester moiety present in 1,4-dihydropyridine calcium channel modulating compounds 16-20 is not a suitable NO donor moiety because the percent nitric oxide released upon in vitro incubation with either L-cysteine, rat serum, or pig liver esterase was less than 1%.