Effect of SIN-1 in rat ventricular myocytes: interference with beta-adrenergic stimulation

Life Sci. 2002 Jun 7;71(3):287-97. doi: 10.1016/s0024-3205(02)01625-9.

Abstract

We have examined the effects of the nitric oxide (NO) donor, 3-morpholino-sydnonimine (SIN-1), on Ca(2+) transients, L-type Ca(2+) current (I(Ca,L)), and cGMP/cAMP content in electrically-stimulated rat ventricular myocytes in the absence and presence of the beta-adrenergic stimulation with isoproterenol. SIN-1 had no effect at low concentrations, but decreased the amplitude of electrically-induced Ca(2+) transients at higher concentrations. SIN-1 attenuated the increase in Ca(2+) transients induced by isoproterenol in a concentration-dependent manner. SIN-1 Also reduced the amplitude of caffeine-induced Ca(2+) transients, and the increase in I(Ca,L) induced by isoproterenol. These effects of SIN-1 were associated with an increased cGMP and a decreased cAMP content in ventricular myocytes in either the absence or presence of isoproterenol. These data suggest that the inhibitory effect of SIN-1 on basal and beta-adrenergic stimulated Ca2+ signal in ventricular myocytes could be due to the depression in the SR function and I(Ca,L), possibly mediated by a cGMP/cAMP-dependent mechanism. Taken together, the present study supports the idea that NO acts as an inhibitory modulator of the cardiac function during pathological conditions associated with an abnormal production of NO such as septic shock.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeine / pharmacology
  • Calcium / metabolism*
  • Calcium Channels / drug effects
  • Calcium Channels / physiology
  • Cyclic AMP / metabolism
  • Cyclic GMP / metabolism
  • Drug Interactions
  • Heart Ventricles / cytology
  • Heart Ventricles / drug effects
  • In Vitro Techniques
  • Molsidomine / analogs & derivatives
  • Molsidomine / pharmacology*
  • Myocardium / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, beta / metabolism*
  • Vasodilator Agents / pharmacology

Substances

  • Calcium Channels
  • Receptors, Adrenergic, beta
  • Vasodilator Agents
  • Caffeine
  • linsidomine
  • Molsidomine
  • Cyclic AMP
  • Cyclic GMP
  • Calcium