title: Endotoxin-induced cardiac depression is associated with decreased cardiac dihydropyridine receptors in rabbits.
abstract: 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.
authors.affiliation: Department of Medicine, Department of Veterans Affairs Medical Center, San Diego, California 92161, USA.
authors.forename: W Y
authors.initials: WY
authors.lastname: Lew
authors.forename: S
authors.initials: S
authors.lastname: Yasuda
authors.forename: T
authors.initials: T
authors.lastname: Yuan
authors.forename: H K
authors.initials: HK
authors.lastname: Hammond
mesh_terms: 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
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D008070:Lipopolysaccharides; D014316:Tritium; D017275:Isradipine