Ethanol reduces cardiac myocyte function through activation of the nitric oxide-cyclic GMP pathway

Harvey R. Weiss, Todd Haim, Qihang Zhang, Yakir Vaks

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

We tested the hypothesis that low-dose ethanol would reduce cardiac myocyte function through increased production in the nitric oxide/cyclic GMP signal transduction pathway, rather than reduced degradation. Ventricular myocytes were isolated from the hearts of 9 rabbits. Myocyte function was studied using a video-edge detector and cyclic GMP levels were measured by radioimmunoassay. Cells were administered 5 and 10 mmol/l ethanol alone or after 10-6 mol/l NG-nitro-L-arginine methyl ester (L-NAME, nitric oxide synthase inhibitor), 10-6mol/l 1H-[1,2,4]oxadiazolo[4,3a]quinoxalin-1-one (ODQ, soluble guanylyl cyclase inhibitor) or 10-5mol/l zaprinast (cyclic GMP phosphodiesterase inhibitor). Ethanol (10 mmol/l) significantly decreased percent shortening from 10.0 ± 0.9 to 6.0 ± 0.2%. Similar decrements occurred in the maximum rate of shortening and relaxation. After L-NAME or ODQ, the decrements in percent shortening, maximum rate of shortening and relaxation caused by ethanol were not significant. After zaprinast, ethanol significantly decreased the maximum rate of shortening and relaxation and percent shortening to 4.3 ± 0.5. Ethanol (10 mmol/l) significantly increased cyclic GMP from 403 ± 121 to 529 ± 128 fmol/105 myocytes. Both L-NAME and ODQ lowered cyclic GMP, and ethanol did not affect cyclic GMP after either. Zaprinast raised cyclic GMP, as did its combination with 10 mmol/l ethanol (653 ± 120). Thus, ethanol both reduced myocyte function and increased cyclic GMP. Blocking nitric oxide production or guanylyl cyclase activity prevent these effects of ethanol, while blocking cyclic GMP degradation did not. This suggests that ethanol acts as a nitric oxide stimulator in ventricular myocytes leading to reduced function and increased cyclic GMP.

Original languageEnglish (US)
Pages (from-to)59-66
Number of pages8
JournalPharmacology
Volume67
Issue number2
DOIs
StatePublished - 2003

All Science Journal Classification (ASJC) codes

  • Pharmacology

Keywords

  • Alcohol
  • Cyclic GMP
  • Ethanol
  • Guanylyl cyclase
  • Myocyte function
  • Nitric oxide synthase
  • Phosphodiesterase
  • Rabbit

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