Transforming growth factor-beta 1 modulates angiotensin II-induced calciumrelease in vascular smooth muscle cells from spontaneously hypertensive rats

Objectives To investigate the role of transforming growth factor-beta 1 (TG F-beta 1) on Ca2+-dependent mechanisms elicited by angiotensin II in aortic vascular smooth muscle cells (VSMC) of Wistar-Kyoto (WKY) rats and spontan eously hypertensive rats (SHR). Methods Ca-i(2+) release induced by angiotensin II (1 mu mol/ l) was studie d in cultured VSMC isolated from the aortas of 6-week-old WKY rats and SHR. Intracellular Ca2+ (Ca-i(2+)) was assessed in Fura-2 loaded cells using fl uorescent imaging microscopy. Angiotensin II receptors were analysed by bin ding studies. Results Pretreatment of VSMC for 24 h with TGF-beta 1 significantly increas ed angiotensin II-induced Ca-i(2+) mobilization from internal stores in SHR , while Ca2+ influx was not altered, This effect involves tyrosine kinase a nd is not due to an increase in angiotensin II binding sites, or a change i n the affinity of the receptors, By contrast, TGF-beta 1 did not modify the response of VSMC from WKY rats to angiotensin II. Conclusions These results help our understanding of the interactions betwee n the pathways activated by TGF-beta 1 and the G protein-coupled receptor s ignalling pathway, and their role in genetic hypertension. J Hypertens 2000 , 18:733-742 (C) Lippincott Williams & Wilkins.