ENHANCEMENT OF PHOSPHOLIPASE-C-DELTA-1 ACTIVITY IN THE AORTAS OF SPONTANEOUSLY HYPERTENSIVE RATS

Spontaneously hypertensive rats (SHR), which develop hypertension appr oximately 10 weeks after birth, are considered to provide a good anima l model for human essential hypertension. We report here that the abno rmal activation of phospholipase C-delta-1 (PLC-delta-1) may be one of the main causes of hypertension. Levels of the second messengers inos itol 1,4,5-triphophate and diacylglycerol are found to be higher in th e aortas of 12-week-old SHR than in age-matched normotensive Wistar-Ky oto rats (WKY), although the levels in the aortas of 7-week-old SHR, w hich 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 fro m 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 t he 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+ c oncentration than that of age-matched WKY. These results suggest that the abnormal enhancement of PLC-delta-1 activity is responsible for ac cumulation of inositol 1,4,5-trisphosphate and diacylgycerol, leading to continuous hypertonicity of vascular smooth muscle in SHR. The acti vity of PLC-delta-1 in the aortas of 12-week-old SHR is significantly higher at low Ca2+ concentration than that of normotensive WKY.