Differential ontogeny of in vitro vascular responses to three categories of calcium channel antagonists in rats.
We examined the ontogeny of relaxation responses to three categories of calcium channel antagonists, represented by verapamil, diltiazem, and nifedipine, for both potential-operated (KCl-mediated) and receptor-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 force-displacement transducer to measure isometric tension. Endothelium intact vessels at optimal passive force were exposed to a single ED50 of isotonic KCl or NE, equilibrium contraction was measured, then vessels were washed and exposed for 30 min to 1 microM verapamil, 1 microM diltiazem, or 0.1 microM nifedipine, followed by another dose of KCl or NE. Verapamil and diltiazem demonstrated significant (p less than 0.05) age-related increases in effectiveness for blocking KCl-mediated contraction [(% reduction of control contraction +/- SEM) (Verapamil: 2-3 d, 67.7 +/- 4.2; 1 wk, 72.5 +/- 1.8; 12 wk, 89.5 +/- 1.0. Diltiazem: 2-3 d, 64.6 +/- 2.9; 1 wk, 73.5 +/- 3.0; 12 wk, 83.1 +/- 1.8]. Nifedipine was equally effective at all ages: 2-3 d, 85.6 +/- 1.3; 1 wk, 90.0 +/- 1.6; and 12 wk, 91.3 +/- 1.4. Verapamil and diltiazem also showed significant age-related increases in effectiveness for blocking NE-mediated contraction (Verapamil: 2-3 d, 6.2 +/- 3.9; 1 wk, 28.0 +/- 4.8; 12 wk, 44.1 +/- 6.0. Diltiazem: 2-3 d, 8.0 +/- 3.1; 1 wk, 20.5 +/- 3.9; 12 wk, 46.5 +/- 4.8).(ABSTRACT TRUNCATED AT 250 WORDS)
Kullama
L K
LK
Department of Pediatrics, Kapiolani Medical Center for Women and Children, Honolulu, Hawaii.
Balaraman
V
V
Claybaugh
J R
JR
Ichimura
W M
WM
Pichoff
B E
BE
Nakamura
K T
KT
D000367:Age Factors; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000145:classification / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D004110:Diltiazem / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine