Responses to calcium and binding of 3H-nimodipine in the atrioventricular node, atria, and ventricles of mature and old male Fischer 344 rats.
To determine whether aging alters cardiac calcium dose responses or dihydropyridine receptor density or affinity, we performed (a) calcium (Ca2+) dose-response studies (3-5 mM) in Langendorff perfused hearts from 12 mature (4-7 month) and 12 old (23-27 month) Fischer 344 rats, and (b) quantitative autoradiography experiments with 3H-nimodipine (50-3,000 pM) in 20-microns tissue sections containing the compact AV node from hearts of eight mature and eight old F344 rats. Baseline AA interval, AV conduction time, AV Wenckebach block cycle length, and QRS duration were prolonged in isolated hearts from old compared with mature rats. In contrast, neither left ventricular developed pressure nor peak dP/dt was altered by age. Perfusion with increasing concentrations of Ca2+ produced decreased coronary perfusion (p < 0.001) without age-related alterations in AA intervals, AV conduction times, dP/dt, or left ventricular developed pressure. No age-related differences in AV node 3H-nimodipine binding (Bmax: mature, 1.35 +/- 0.41 fmol/mm2; old, 1.33 +/- 0.43 fmol/mm2) or affinity (Kd: mature, 915 +/- 375 pM; old, 973 +/- 369 pM) were detected. Similarly, no age-related differences in 3H-nimodipine receptor number or affinity were detected in left and right ventricular or atrial tissue. Total protein in atrial and ventricular tissue was unchanged with age. However, left atrial and left ventricular isolated membrane protein was significantly lower in senescent compared with mature rat hearts (left ventricle: mature, 49.4 +/- 8.7 mg/g; old, 40.9 +/- 3.5 mg/g; p < 0.05; left atria: mature, 36 +/- 9 mg/g; old, 28 +/- 3 mg/g; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Kusumoto
F M
FM
Cardiology Division, Lovelace Medical Center, Albuquerque, New Mexico 87108, USA.
Capili
H
H
Sniezek
M J
MJ
Schwartz
J B
JB
D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects* / Q000378:metabolism; D001345:Autoradiography; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020746:Calcium Channels, L-Type; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D006329:Heart Conduction System / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007553:Isotope Labeling; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009553:Nimodipine / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011950:Receptors, Cholinergic / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D008565:Membrane Proteins; D011950:Receptors, Cholinergic; D014316:Tritium; D009553:Nimodipine; D002118:Calcium