Enhancement of phospholipase C delta 1 activity in the aortas of spontaneously hypertensive rats.
Spontaneously hypertensive rats (SHR), which develop hypertension approximately 10 weeks after birth, are considered to provide a good animal model for human essential hypertension. We report here that the abnormal activation of phospholipase C delta 1 (PLC-delta 1) may be one of the main causes of hypertension. Levels of the second messengers inositol 1,4,5-trisphosphate and diacylglycerol are found to be higher in the aortas of 12-week-old SHR than in age-matched normotensive Wistar-Kyoto rats (WKY), although the levels in the aortas of 7-week-old SHR, which have normal blood pressure, are the same as in WKY. Moreover, PLC activity is also higher in the aortas of 12-week-old SHR. Judging from Western blot analysis and immunoabsorption of PLCs, this activation is found to be due to that of PLC-delta 1. PLC-delta 1 from rat aorta is expressed significantly from 7 to 12 weeks, which correlates with the development of hypertension in SHR. The activity of PLC-delta 1 in the aortas of 12-week-old SHR is more markedly activated at low Ca2+ concentration than that of age-matched WKY. These results suggest that the abnormal enhancement of PLC-delta 1 activity is responsible for accumulation of inositol 1,4,5-trisphosphate and diacylglycerol, leading to continuous hypertonicity of vascular smooth muscle in SHR. The activity of PLC-delta 1 in the aortas of 12-week-old SHR is significantly higher at low Ca2+ concentration than that of normotensive WKY.
Kato
H
H
Department of Biosignal Research, Tokyo Metropolitan Institute of Gerontology, Japan.
Fukami
K
K
Shibasaki
F
F
Homma
Y
Y
Takenawa
T
T
D019870:1-Phosphatidylinositol 4-Kinase; D000375:Aging / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000201:enzymology* / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002853:Chromatography, Liquid; D004075:Diglycerides / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D006973:Hypertension / Q000201:enzymology* / Q000378:metabolism; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D010770:Phosphotransferases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
D004075:Diglycerides; D007295:Inositol Phosphates; D007527:Isoenzymes; D012333:RNA, Messenger; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase; D010738:Type C Phospholipases; D002118:Calcium