Alterations in Receptor-Mediated Activation of Phospholipase A2 in DAHL Salt-Sensitive Rats
In this study, the subcellular mechanism of impaired prostacyclin (PGI2) synthesis in the vascular system of Dahl salt-sensitive (Dahl S) rats was investigated. Arachidonate liberation in response to PDGF or bradykinin was decreased in cultured aortic smooth muscle cell (VSMC) from Dahl S rats, comp...
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Published in | Hypertension Research Vol. 16; no. 2; pp. 105 - 111 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
The Japanese Society of Hypertension
1993
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Subjects | |
Online Access | Get full text |
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Summary: | In this study, the subcellular mechanism of impaired prostacyclin (PGI2) synthesis in the vascular system of Dahl salt-sensitive (Dahl S) rats was investigated. Arachidonate liberation in response to PDGF or bradykinin was decreased in cultured aortic smooth muscle cell (VSMC) from Dahl S rats, compared with Dahl salt-resistant (Dahl R) rats. Phospholipase C (PIP2-PLC) activity was lowered and the inositol 1, 4, 5-triphosphate content was also decreased in the VSMC from Dahl S rats. In fact, cytosolic calcium levels in basal and angiotensin-II stimulated conditions were significantly decreased in VSMC from Dahl S rats, compared with those in Dahl rats. There was no difference, however, in phospholipase A2 (PLA2) activity in the two strains. Moreover, the PLA2 enzyme properties, e.g., its Ca2+ requirement, pH profile, Km value and Vmax, were equal in Dahl S and Dahl R rats. The level of functional PLA2 messenger RNA was found to be greater in the VSMC from Dahl S rats. Similarly, PGI2 synthesis was reduced in Dahl S rats and this was associated with an unaltered PLA2 concentration and decreased PIP2-PLC activity in the arterial wall. Thus, these data indicate that dysfunction of receptor-mediated PLA2 activation is responsible for altered PGI2 synthesis in Dahl S rats. This finding is likely mediated by a decrease in phosphoinositides metabolism. (Hypertens Res 1993; 16: 105-111) |
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ISSN: | 0916-9636 1348-4214 |
DOI: | 10.1291/hypres.16.105 |