IL-1 inhibits β-adrenergic control of cardiac calcium current: Role of L- arginine/nitric oxide pathway

Modulation of the β-adrenergic control of cardiac L-type Ca²⁺ current (I(Ca)) by human recombinant interleukin-1β (IL-1) was examined in adult guinea pig ventricular myocytes using the whole cell voltage-clamp technique. I(Ca) was elicited in Cs⁺-loaded myocytes by depolarizing pulses from a holding potential of -40 mV. Isoproterenol (0.01 and 1 μM) exposed to myocytes pretreated with 1 ng/ml IL-1 evoked a significantly smaller increase in I(Ca) density compared with control cells. This IL-1-mediated decrease in β-responsiveness was usually observed with pretreatment periods of > 1 h and varied as a function of the L-arginine concentration of the pretreatment medium. In addition, it was prevented by 1) IL-1 receptor antagonist, 2) substituting D-arginine for L-arginine, or 3) incubating cells with the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine. Thus the present data illustrate that IL-1 significantly alters the β-adrenergic control of cardiac Ca²⁺ channels by cellular mechanisms that involve the activation of nitric oxide synthase. These mechanisms may play a role in altering ventricular function during cytokine-mediated inflammatory processes affecting the heart.