Endotoxin-induced cardiac depression is associated with decreased cardiac dihydropyridine receptors in rabbits.
Endotoxin depresses left ventricular (LV) contractility independently of alterations in loading conditions, acidosis, or hypoxia (Hung and Lew, 1993a). We evaluated if endotoxin-induced LV depression is associated with a decrease in functional L-type calcium channels, as reflected by the number of dihydropyridine receptors measured by [3H]-PN200-110 binding. New Zealand white rabbits were instrumented with sonomicrometers to measure the end-systolic pressure-volume relationship after i.v. saline (group 1, n = 6), 5 micrograms/kg endotoxin (group II, n = 6), or 10 micrograms/kg endotoxin (group III, n = 6). The end-systolic volume (ESV) measured at a matched end-systolic pressure did not change significantly over 6 h in group I (ESV changed by < 5 +/- 2% S.E.) and group II (ESV changed by < 3 +/- 2%), but increased markedly in group III (ESV increased 70 +/- 24%, P < 0.05), indicating LV systolic depression. We measured [3H]-PN200-110 binding in crude membrane homogenates from the left ventricle. There was a dose-dependent decrease in Bmax: 75 +/- 5 fmol/mg protein in group I, 62 +/- 3 fmol/mg in group II, and 56 +/- 5 fmol/mg in group III (P = 0.02 by ANOVA). Since the majority of dihydropyridine receptors are functional L-type calcium channels in rabbits (Lew et al., 1991), we conclude that a decreased number of dihydropyridine receptors contributes to endotoxin-induced LV depression.
Lew
W Y
WY
Department of Medicine, Department of Veterans Affairs Medical Center, San Diego, California 92161, USA.
Yasuda
S
S
Yuan
T
T
Hammond
H K
HK
D000818:Animals; D015220:Calcium Channels / Q000096:biosynthesis* / Q000502:physiology; D020746:Calcium Channels, L-Type; D015536:Down-Regulation; D004926:Escherichia coli; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D017275:Isradipine / Q000378:metabolism; D007700:Kinetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011817:Rabbits; D011869:Radioligand Assay; D013599:Systole / Q000187:drug effects; D014316:Tritium; D016277:Ventricular Function, Left / Q000187:drug effects
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D008070:Lipopolysaccharides; D014316:Tritium; D017275:Isradipine