TRANSFORMING GROWTH-FACTOR BETA(1) MODULATES ANGIOTENSIN-II-INDUCED CALCIUM INFLUX IN VASCULAR SMOOTH-MUSCLE

The modulatory effects of transforming growth factor beta(1) (TGF beta (1)) on the angiotensin II (Ang II)-induced increase in cytosolic free calcium concentration ([Ca2+](i)) were investigated in vascular smoot h muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and n ormotensive Wistar-Kyoto rats (WKY). [Ca2+](i) in VSMC was measured us ing the fluorescent dye fura-2. When TGF beta(1) was applied 30s prior to Ang II, the Ang II-induced [Ca2+](i) increase was significantly en hanced in VSMC from SHR (P < 0.05 compared to control), whereas after the preincubation with TGF beta(1) for 30 min, the Ang II-induced [Ca2 +](i) increase was significantly reduced in VSMC from both strains. Us ing the manganese-quenching technique, it was confirmed that short-ter m exposure to TGF beta(1) enhanced the Ang II-induced trans-plasma-mem brane calcium influx in SHR. The inhibition of protein kinase C by cal phostin C abolished the stimulatory effect of TGF beta(1) on the Ang I I-induced [Ca2+](i) increase. It is concluded that TGF beta(1) modulat es the Ang II-induced calcium handling in VSMC.