Negative Inotropic Effects of Cytokines on the Heart Mediated by Nitric Oxide

TLDR

The study examined how pro‑inflammatory cytokines directly affect mammalian heart contractility. Cytokines TNFα, IL‑6, and IL‑2 dose‑dependently and reversibly reduced hamster papillary muscle contractility, an effect blocked by the NOS inhibitor L‑NMMA and reversed by L‑arginine, indicating myocardial nitric‑oxide synthase mediates the negative inotropic action and suggesting therapeutic targeting of this pathway.

Abstract

The direct effects of pro-inflammatory cytokines on the contractility of mammalian heart were studied. Tumor necrosis factor α, interleukin-6, and interleukin-2 inhibited contractility of isolated hamster papillary muscles in a concentration-dependent, reversible manner. The nitric oxide synthase inhibitor N G -monomethyl-L-arginine (L-NMMA) blocked these negative inotropic effects. L-Arginine reversed the inhibition by L-NMMA. Removal of the endocardial endothelium did not alter these responses. These findings demonstrate that the direct negative inotropic effect of cytokines is mediated through a myocardial nitric oxide synthase. The regulation of pro-inflammatory cytokines and myocardial nitric oxide synthase may provide new therapeutic strategies for the treatment of cardiac disease.