Differential Ontogeny of in Vitro Vascular Responses to Three Categories of Calcium Channel Antagonists in Rats

Abstract

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...

Rat pulmonary arterial smooth muscle myosin light chain kinase and phosphatase activities decrease with age

“…Although no developmental data have been previously reported for the pulmonary artery in mammals, our findings are in keeping with the MLCK content of the sheep aorta where a significant increase was observed from fetal to adult life (3). Such an increase in the pulmonary and systemic vascular MLCK content likely ac- counts for the greater force observed in the adult when compared with the fetal vessels as documented in the pulmonary artery in this study and in the aorta by others (23). Yet a significant age difference in this enzyme-specific activity was noted for the pulmonary artery, but not aorta, indicating that prenatally a greater activity per unit mass is present in this tissue.…”

“…Maturational changes in the pulmonary and systemic vascular smooth muscle contraction and relaxation potential have been reported by us in sheep (6,9) and by others in the rabbit (19,26) and rat thoracic aorta (23). To the best of our knowledge this is the first developmental study of the rat pulmonary artery smooth muscle mechanical properties and its key cell enzymes responsible for contraction and relaxation.…”