Sequential Changes in Autonomic Regulation of Cardiac Myocytes after In Vivo Endotoxin Injection in Rat

Abstract

International audienceWe report that in vivo injection of endotoxin (EDTX, 6 mg · kg− 1) induces cardiovascular alterations in rats that closely mimic the clinical situation, as assessed by in vivo hemodynamic measurements in anesthetized and conscious, chronically instrumented animals. The patch-clamp technique was used to characterize the L-type calcium current (ICa) and its autonomic regulation in isolated cardiac myocytes. The density of ICa progressively decreased at 12 and 36 h after EDTX injection. However, the dihydropyridine ( ± )Bay K 8644 (100 nM) enhanced ICa to levels similar to those in control and EDTX-treated myocytes. In addition, the net stimulatory effect of a β -adrenergic agonist (isoproterenol) on ICa was increased 12 h after EDTX injection. This change in the β -adrenergic effect declined 24 h later. The potentiation in the β -adrenergic stimulation of ICa was mimicked by L858051 (10 μ M), a direct activator of adenylyl cyclase, but not by IBMX (200 μ M), a phosphodiesterase inhibitor. Besides, the antiadrenergic effect of acetylcholine on ICa was unchanged 12 h after EDTX injection, but increased 36 h after EDTX injection. These results support the hypothesis that time-dependent changes in the adenylyl cyclase pathway in cardiac myocytes may contribute, via the autonomic regulation of ICa, to the severity of myocardial dysfunction during sepsis