Cerebrovascular alterations in pressure and protein kinase C-mediated constriction in Dahl salt-sensitive rats
- 1 July 2002
- journal article
- research article
- Published by Wolters Kluwer Health in Journal Of Hypertension
- Vol. 20 (7) , 1355-1363
- https://doi.org/10.1097/00004872-200207000-00022
Abstract
Dahl salt-sensitive (DSS) rats fed an 8.7% sodium chloride diet from weaning spontaneously developed hypertension and a 50% mortality rate by 5 weeks. Before death the rats exhibited behavioural signs of stroke and disruption of the blood–brain barrier. To test the hypothesis that rats exhibiting stroke had middle cerebral arteries (MCAs) that had lost the ability to constrict in response to pressure, and to assess whether this defect was associated with abnormalities in protein kinase C (PKC)-mediated constriction. MCAs were sampled from DSS rats before and after stroke and from Dahl salt-resistant (DSR) rats fed 8.7% NaCl. Constrictions in response to a 100 mmHg pressure step and to PKC activation by phorbol dibutyrate (PDB) (0.1 μmol/l) in the presence of nifedipine (3 μmol/l) were measured. MCAs from DSS rats after stroke constricted in response to vasopressin but were unable to constrict in response to pressure or PDB in the presence of nifedipine, whereas those from DSS rats before stroke and from DSR rats constricted in response to all the stimuli. The PKC inhibitors, chelerythrine (12 μmol/l) and bisindolylmaleimide (5 μmol/l) inhibited constrictions in response to pressure and to PDB in the presence of nifedipine. Constriction of the MCA in response to pressure is dependent on functional PKC signalling. Development of stroke in DSS rats fed a high-salt diet is associated with an inability of the MCAs to constrict in response to pressure, possibly because of the presence of an incompetent PKC system. The inability to constrict in response to pressure may cause blood flow abnormalities that contribute to disruption of the blood–brain barrier in these rats.Keywords
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