Skip to main content
  • Poster presentation
  • Published:

Anti-adrenergic effects of ranolazine in isolated rat aorta

Introduction

Ranolazine, a piperazine derivative, is used as an anti- anginal drug to treat patients with chronic angina in clinical practice [1] and may improve coronary blood flow by reducing compression effects of ischemic contracture, and by improving endothelial function [2],[3]. In the present study we investigate the vascular effects of ranolazine on the endothelium, adrenergic system and Ca2+ in isolated rat aorta.

Methods

Rat aortic segments (3 mm long) with and without endothelium were mounted for isometric tension recording in organ baths containing Krebs-Henseleit solution. Electrical field stimulation (2, 4 and 8 Hz, 20 V, 0.25 ms duration for 30 seconds) was provided by a Grass S88 stimulator via two platinum electrodes positioned on each side and parallel to the axis of the aortic segment. Concentration- response curves of ranolazine (10−7 to 10−4 M) were obtained in a cumulative manner using endothelin-1, noradrenaline, thromboxane A2 and KCl as constrictor agents.

Results

The contractile responses to electrical field stimulation were abolished by tetrodotoxin, guanethidine and prazosin, indicating that the contractile effect is due to the action of noradrenaline on alpha adrenoreceptors. Ranolazine diminished (P < 0.05) neurogenic adrenergic contractions induced by electrical field stimulation in aortic rings with and without endothelium. Ranolazine produced concentration-dependent relaxation in rings precontracted with noradrenaline (Emax 86 ± 6%, n = 10; P < 0.05) but not in rings precontracted with endothelin-1, thromboxane A2 and KCl. Neither L-NAME (10−4 M), an inhibitor of nitric oxide synthase, nor indomethacin (10−5 M), an inhibitor of cyclooxygenase, modified the relaxation induced by ranolazine. The calcium antagonist nifedipine (10−6 M) reduced the relaxation induced by ranolazine.

Conclusion

These results indicate that ranolazine diminished the contractile response induced by adrenergic stimulation, suggesting an effect as an adrenergic blocker. The relaxant effects of ranolazine on rat aortic vessels is not dependent on the endothelium-derived factors (nitric oxide or dilator prostanoids) but involves an interference with the entry of calcium through dihydropyridine calcium channels.

References

  1. Chaitman BR: Circulation. 2006, 113: 2462-2472. 10.1161/CIRCULATIONAHA.105.597500

    Article  PubMed  Google Scholar 

  2. Stone PH, et al.: J Am Coll Cardiol. 2010, 56: 934-942. 10.1016/j.jacc.2010.04.042

    Article  CAS  PubMed  Google Scholar 

  3. Deshmukh SH, et al.: Coron Artery Dis. 2009, 20: 343-347. 10.1097/MCA.0b013e32832a198b

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marchio, P., Mauricio, M., El Amrani, F. et al. Anti-adrenergic effects of ranolazine in isolated rat aorta. Crit Care 18 (Suppl 1), P184 (2014). https://doi.org/10.1186/cc13374

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/cc13374

Keywords