Abnormal Ca2+ signalling in vascular endothelial cells from spontaneously hypertensive rats: role of free radicals.

Abstract

OBJECTIVE:

To test the hypothesis that the Ca2+ signal transduction process in endothelial cells from genetically hypertensive rats (SHR) is affected by an overproduction of free radicals.

METHODS:

The Ca2+ response to the inositol 1,4,5-triphosphate (IP3) mobilizing agonist, ATP, was measured using the fluorescent probe, fura-2, in endothelial cells from Sprague-Dawley rats, and in young and age-matched genetically hypertensive rats (SHR). The effect of free radicals and reducing agents on the intracellular release of Ca2+ and IP3productionwas determined in resting and ATP-stimulated cells. Experiments were also performed to compare the level of expression and enzymatic activity of catalase and superoxide dismutase (SOD) in endothelial cells from SHR and Sprague-Dawley rats.

RESULTS:

The exposure of aortic endothelial cells from Sprague-Dawley rats to the free-radical generating system, hypoxanthine + xanthine oxidase (HX/XO), caused a time- and concentration-dependent inhibition of the ATP-induced Ca2+ response. A similar HX/XO-dependent inhibition was also observed in Sprague-Dawley cells stimulated with the endoplasmic reticulum Ca2+-ATPase inhibitor, thapsigargin. Incubation with the antioxidative enzymes, catalase and SOD, had no effect on the ATP-induced Ca2+ release in Sprague-Dawley cells, but led to a strong increase in the internal release of Ca2+ in cells from adult (12 weeks old) or young (3 weeks old) SHR. The effect of antioxidants was not related either to an enhancement of the ATP-induced production of IP3, or to a lower expression and activity of SOD and catalase.

CONCLUSION:

The present work provides evidence that the Ca2+ signalling process in SHR endothelial cells is affected by an overproduction of free radicals, resulting in a depletion of releasable Ca2+ from IP3-sensitive and insensitive Ca2+ pools. These results point towards a beneficial action of antioxidants on Ca2+ signalling in endothelial cells from models of hypertension.

• Authors: L Pogan, L Garneau, P Bissonnette, L Wu, R Sauvé
• Journal: Journal of hypertension (J Hypertens) Vol. 19 Issue 4 Pg. 721-30 (Apr 2001) ISSN: 0263-6352 [Print] England
• PMID: 11330875 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Free Radicals
• Adenosine Triphosphate
• Catalase
• Superoxide Dismutase

Topics

• Adenosine Triphosphate (pharmacology)
• Animals
• Calcium Signaling (drug effects)
• Catalase (metabolism, pharmacology)
• Cells, Cultured
• Endothelium, Vascular (drug effects, pathology, physiopathology)
• Free Radicals (metabolism)
• Hypertension (pathology, physiopathology)
• Male
• Rats
• Rats, Inbred SHR (physiology)
• Rats, Sprague-Dawley (physiology)
• Superoxide Dismutase (metabolism, pharmacology)