ABSTRACT. We examined the ontogeny of relaxation function may vary depending on the site of binding within responses to three categories of calcium channel antagothe calcium channel. (Pediatr Res 29: 278-281, 1991) nists, represented by verapamil, diltiazem, and nifedipine, for both potential-operated (KCI-mediated) and receptorAbbreviations operated channels [norepinephrine (NE)-mediated] in rat thoracic aorta. Aortic rings from 2-to 3-d, 1-wk, and 12-wk-old Sprague Dawley rats were mounted in an organ bath, bathed in Krebs' solution, and connected to a forcedisplacement transducer to measure isometric tension. Endothelium intact vessels at optimal passive force were exposed to a single EDso of isotonic KC1 or NE, equilibrium contraction was measured, then vessels were washed and exposed for 30 min to 1 pM verapamil, 1 pM diltiazem, or 0.1 pM nifedipine, followed by another dose of KC1 or NE.Verapamil and diltiazem demonstrated significant (p c 0.05) age-related increases in effectiveness for blocking KCI-mediated contraction [(% reduction of control contraction f SEM) (Verapamil: 2-3 d, 67.7 f 4.2; 1 wk, 72.5 f 1.8; 12 wk, 89.5 f 1.0. Diltiazem: 2-3 d, 64.6 f 2.9; 1 wk, 73.5 f 3.0; 12 wk, 83.1 f: 1.81. Nifedipine was equally effective at all ages: 2-3 d, 85.6 f 1.3; 1 wk, 90.0 f 1.6; and 12 wk, 91.3 f 1.4. Verapamil and diltiazem also showed significant age-related increases in effectiveness for blocking NE-mediated contraction (Verapamil: 2-3 d, 6.2 f 3.9; 1 wk, 28.0 f 4.8; 12 wk, 44.1 f 6.0. Diltiazem: 2-3 d, 8.0 f 3.1; 1 wk, 20.5 f 3.9; 12 wk, 46.5 f 4.8). Again, nifedipine was equally effective at all ages: 2-3 d, 42.0 f 6.8; 1 wk, 35.8 f 3.9; and 12 wk, 37.5 f 3.2. In summary, for the categories of calcium channel antagonists that interact at the phenylalkylamine (verapamil) and benzothiazepine (diltiazem) binding sites, there were age-related increases in effectiveness for blocking both potentialoperated and receptor-operated channels. However, for nifedipine, which binds to the 1,4-dihydropyridine binding site, no maturational change was observed. These results suggest that the ontogeny of calcium channel antagonists' We have previously (8) demonstrated the ontogeny of the concentration-dependent response in thoracic aortic rings among 2-d-, 1-wk-, and 1 Zwk-old rats for both potential-mediated (KClinduced) and receptor-mediated (NE-induced) contraction. Thus, calcium channel function is present from 2 d of age with perhaps increasing physiologic function during development. However, many aspects of calcium channel function during ontogeny are unknown. We therefore designed the present study to examine one aspect of calcium channel function, viz. the ontogeny of responses to three categories of calcium channel antagonists for KCI-and NE-mediated contraction in rat aorta. The objectives were 3-fold: to determine if there were 1) agerelated differences in response to selective calcium channel antagonists; 2) differential effects among the three categories of calcium channel antagonists; and 3 ) differe...