Abstract
BackgroundIn the present study we have analyzed the mechanisms of calcium entry and mobilization in platelets obtained from rats chronically treated with the nitric oxide synthesis inhibitor, N-nitro L-arginine methyl ester [L-NAME, 40 mg/kg/day, 5 days). The platelets were obtained the day of the experiment, washed and loaded with fura-2. The intracellular calcium levels were determined in suspension of cells by means of fluorescence spectroscopy.ResultsBasal calcium levels were always elevated in the platelets of the L-NAME-treated rats, both in the presence and in the absence of extracellular calcium. The administration of thrombin in the absence and in the presence of extracellular calcium induced important elevations in calcium levels that were always of greater magnitude in the platelets of the L-NAME-treated rats than in those of the controls. The addition of calcium to thapsigargin-treated platelets produced a massive elevation in calcium levels in both groups that was significantly greater in the platelets obtained from the hypertensive rats than in those of the controls.ConclusionsIt is concluded that the arterial hypertension induced by the reduction of nitric oxide alters the regulation of platelet calcium levels so that elevated baseline levels and calcium entry and mobilization are enhanced. This could be the result of direct or indirect effects of the lack of nitric oxide synthesis in platelets or in other tissues.
Highlights
In the present study we have analyzed the mechanisms of calcium entry and mobilization in platelets obtained from rats chronically treated with the nitric oxide synthesis inhibitor, N-nitro L-arginine methyl ester [L-NAME, 40 mg/kg/day, 5 days)
Resting calcium levels were always elevated in the platelets of the LNAME-treated rats, both in the presence (155 ± 10 nM in these hypertensive rats and 76 ± 8 nM in the controls) and in the absence of extracellular calcium (154 ± 7 nM and 70 ± 4 nM, respectively)
The area under the curve (AUC) measured during the first 60 seconds after the administration of the 0.3 U dose was significantly greater in the platelets of the hypertensive rats (866.5 ± 102.4 units) than in those of the controls (513.53 ± 64.9 units)
Summary
In the present study we have analyzed the mechanisms of calcium entry and mobilization in platelets obtained from rats chronically treated with the nitric oxide synthesis inhibitor, N-nitro L-arginine methyl ester [L-NAME, 40 mg/kg/day, 5 days). Platelets were one of the first cell types where the L-arginine-nitric oxide pathway was characterized [6]. Recent studies have suggested that NO is able to interfere with the regulation of calcium levels in platelets [7] and in other cell types. We hypothesized that the reduction in NO levels brought about by the chronic inhibition of NO that induces an arterial hypertensive state would induce an elevation in platelet calcium concentration. In order to test this hypothesis, we have performed experiments on platelets obtained from L-NAME-treated hypertensive rats, by using fluorescence spectroscopy
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