ABSTRACT
Angiotensin II (Ang II) induces a rapid increase in mitogen-activated protein kinase (MAPK) activity through the Ang II type 1 receptor in cultured rat vascular smooth muscle cells (VSMCs). In the present study, we examined the effects of the phospholipase C (PLC) inhibitor U73122, the protein kinase C (PKC) inhibitor GF109203X, and the Ras inhibitor farnesylthiosalicylic acid (FTS) on Ang II-induced activation of p42/p44 MAPKs in cultured VSMCs. Phosphorylation was shown using the Western blot technique with specific phospho-antibodies against MAPK proteins. The PLC inhibitor U73122 abolished the Ang II-induced MAPK activity, while the PKC inhibitor GF109203X only decreased it. There was also an inhibition observed with the Ras inhibitor, FTS on Ang II-induced MAPK activity. These data suggest that Ang II-induced MAPK phosphorylation through the Ang II type 1 receptor could be mediated by Ras and/or PLC-dependent phosphorylations but not by PKC phosphorylation.
Subject(s)
Angiotensin II/pharmacology , Mitogen-Activated Protein Kinases/metabolism , Muscle, Smooth, Vascular/drug effects , Type C Phospholipases/metabolism , ras Proteins/metabolism , Animals , Blotting, Western , Cells, Cultured , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Estrenes/pharmacology , Farnesol/analogs & derivatives , Farnesol/pharmacology , Indoles/pharmacology , Losartan/pharmacology , Male , Maleimides/pharmacology , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/metabolism , Phosphorylation/drug effects , Protein Kinase C/antagonists & inhibitors , Protein Kinase C/metabolism , Pyrrolidinones/pharmacology , Rats , Rats, Wistar , Receptor, Angiotensin, Type 1/physiology , Salicylates/pharmacology , Time Factors , Type C Phospholipases/antagonists & inhibitors , ras Proteins/antagonists & inhibitorsABSTRACT
Mean platelet volume (MPV), a determinant of platelet function, is a newly emerging risk factor for atherothrombosis. The risk profile of white coat hypertension has not yet been completely clear. The present study was designed to evaluate MPV in white coat hypertensive subjects compared with essential hypertensive patients and normotensive subjects. We selected 36 essential hypertensive patients, 36 white coat hypertensive subjects and 36 normotensive control subjects matched for age, gender, and body mass index. MPV was very significantly higher in essential hypertensives and white coat hypertensives than in normotensives (P < 0.00); it was also higher in essential hypertensives than in white coat hypertensives (P < 0.05). Platelet counts were not different among the study groups (P > 0.05). MPV was positively correlated with ambulatory diastolic blood pressure in essential hypertension and white coat hypertension groups (P < 0.05). In conclusion, our data suggests one possible mechanism by which white coat hypertensive subjects may be at increased cardiovascular risk.
