Calcium channel blockers are widely used to treat cardiovascular disease (CVD) including hypertension. Aging is an independent risk factor for CVD and the use of these blockers increases with aging. The aim of this study was to evaluate the response of resistance mesenteric arteries to nifedipine, verapamil and diltiazem which are chemically unrelated calcium channel blockers. Male F344 rats, aging 2.5-3 months (young) and 22-26 months (old) were used. Animals were sacrificed with an overdose of a mixture of ketamine (140 mg kg−1 I.P.) and xylazine (40 mg kg−1 I.M.). Third order mesenteric arteries were mounted on wire myograph and tension was measured in isometric recording in the presence and absence of different blockers. In all experiments, the viability of arteries was assessed by a contractile response to KCl (60 mM) and the integrity of the endothelium was assessed by a dilator response to acetylcholine (1μM). Arteries were sub-maximally pre-contracted with phenylepherine (PE; 4μM) and then relaxed in a cumulative dose-response manner with nifedipine (0.1-10uM), verapamil or diltiazem (0.1-5 µM) or sodium nitroprusside (SNP; 0.1-10 μM). Values (mean ± s.e.m..; statistically significant difference was calculated using unpaired Student t-test; p < 0.05). Contractions induced by KCl were 10.8±0.6 vs. 10.7±0.7 mN and PE 13±0.5 vs. 12±0.8 mN (young vs. old) were not significantly different. Concentration-response curves to the three calcium channel blockers were shifted to the right in arteries isolated from old rats with statistically significant IC50s. In arteries isolated from old rats compared to young rats, IC50 increased from 3.6 to 11 nM (nifedipine n= 8), 94 to 187 nM (verapamil n=7) and 250 to 400nM (diltiazem, n=12). To investigate that this response was particularly associated with calcium channel blocking, arteries relaxed with SNP in a cumulative dose response (0.1 nM to10 µM) showed no significant difference between young and old groups (n=8). In conclusion, our results suggest that aging reduces the response of mesenteric arteries to the vasodilatory effect of these calcium channel blockers.