Caveolae are identifiable plasma membrane invaginations. The main structural proteins of caveolae are the caveolins (cav-1, -2, and -3). Cav-1 acts as a scaffold protein for signaling proteins, including: ion channels, enzymes, and other ligand receptors like, membrane associated estrogen receptors (ER). Caveolae associated proteins are involved in regulating some of the rapid estrogenic effects of 17-estradiol. One important system related to the activity of ER and caveolae is the rennin-angiotensin system (RAS). Angiotensin II (Ang II) has numerous actions in vascular smooth muscle, including; modulation of vasomotor tone, cell growth, apoptosis, PI3K-Akt activation. Many proteins associated with Caveolae are in closed relation with the scaffolding domain of caveolin-1 (82-101 aa residues), that may acts as a kinase inhibitor. Therefore, to explore the ability of caveolin-1 scaffolding peptide (CSP-1) to regulate Ang II function and analyze the relationship between ER, AT1 and AT2 receptors, we decided to study the effects of CSP-1 on angiotensin II-induced intracellular calcium kinetics and the estradiol effect on this modulation using human smooth muscle cells in culture, calcium concentration measurements, double-immunocytochemistry confocal analysis of receptor expression immunoco-precipitation assays to demonstrate coexpression. We hypothesized that CSP-1 inhibits Ang II-mediated increases in intracellular calcium concentrations by interfering with intracellular signaling including the PI3K/Akt pathway. We also hypothesize that AT2 receptors associate with caveolin-1. Our results show that there is a close association of AT1, AT2, and ER with cav-1 in human arterial smooth muscle cells in culture. CSP-1 inhibits Ang II-induced intracellular signaling.