IL-1 inhibits beta-adrenergic control of cardiac calcium current: role of L-arginine/nitric oxide pathway.
Modulation of the beta-adrenergic control of cardiac L-type Ca2+ current (Ica) by human recombinant interleukin-1 beta (IL-1) was examined in adult guinea pig ventricular myocytes using the whole cell voltage-clamp technique. ICa was elicited in Cs(+)-loaded myocytes by depolarizing pulses from a holding potential of -40 mV. Isoproterenol (0.01 and 1 microM) exposed to myocytes pretreated with 1 ng/ml IL-1 evoked a significantly smaller increase in ICa density compared with control cells. This IL-1-mediated decrease in beta-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 NG-monomethyl-L-arginine. Thus the present data illustrate that IL-1 significantly alters the beta-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.
Rozanski
G J
GJ
Department of Physiology, University of Nebraska College of Medicine, Omaha 68198-4575.
Witt
R C
RC
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D019323:omega-N-Methylarginine
D000319:Adrenergic beta-Antagonists; D015220:Calcium Channels; D007375:Interleukin-1; D011943:Receptors, Adrenergic, beta; D011994:Recombinant Proteins; D005576:Colforsin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D007545:Isoproterenol