Transgenic hypertensive rats show a reduced angiotensin II induced [Ca2+]i response in glomerular mesangial cells

The effects of angiotensin II (Ang II) induced changes of cytosolic free calcium concentration ([Ca2+]i) and growth response were investigated in transgenic TGR(mREN2)27 rats, a strain showing fulminant hypertension after the mouse Ren-2d renin gene has been integrated into its genome, in age-matched normotensive Sprague-Dawley rats (SD), in spontaneously hypertensive rats of the Münster strain (SHR), and in normotensive Wistar-Kyoto rats (WKY). In each strain the Ang II induced changes of [Ca2+]i were measured in cultured glomerular mesangial cells (MC) using the calcium-sensitive fluorescent dye, fura2. Resting [Ca2+]i was not significantly different between the strains tested. The Ang II induced [Ca2+]i rise was significantly less in MC from TGR(mREN2)27 compared to SD (peak level at 200 seconds: 161 +/- 15 nmol/L vs 217 +/- 43 nmol/L; mean +/- SEM; p<0.05). In the absence of external calcium, the Ang II induced [Ca2+]i increase was similar in MC from TGR(mREN2)27 and SD, indicating that the Ang II induced trans-plasma membrane calcium influx but not the calcium release is impaired in TGR(mREN2)27. The arginine vasopressin or endothelin induced [Ca2+]i increase were not significantly different in MC from TGR(mREN2)27 and SD. The Ang II or PDGF induced 3H-thymidine incorporation was not significantly different in MC from TGR(mREN2)27 and SD, indicating that the early growth response to Ang II is not impaired in TGR(mREN2)27. The Ang II induced peak [Ca2+]i increase was significantly enhanced in MC from SHR compared to WKY (215 +/- 30 nmol/L, n=17; vs 161 +/- 35 nmol/L, n=17; p<0.05). It is concluded that TGR(mREN2)27 show a selective defect in the cellular calcium response to Ang II.