Caveolae by interfering internalization of AT1 receptors regulate constrictions of isolated arterioles to Ang II

Abstract

We hypothesized that caveolae regulate Ang II ‐ induced arteriolar constrictions by modulating the internalization of type 1 angiotensin II (Ang II) receptors (AT1R). Thus to assess the functional availability of AT1R, Ang II (10‐8 M) were administered in a repeated fashion (first and second applications) and the diameter of skeletal muscle arterioles (≈150 μm at 80 mmHg) were measured with videomicroscopy. Compared to the first application, Ang II‐induced constrictions were significantly reduced upon the second application (% max. constrictions: 59±3 vs. 37±2, P<0.05). Incubation of arterioles with concanavalin A (0.1 mM for 2 hours), known to inhibit AT1R internalization, had no effect on Ang II‐induced constrictions upon the first application (65±7%), but further significantly diminished constrictions to the second application (9±5%). Incubation of vessels with methyl β‐cyclodextrin (1 mM for 2 hours), known to disrupt caveolae, resulted in maintained Ang II‐induced arteriolar constrictions upon repeated applications (61±3 vs. 69±7, N.S.). We propose that internalization of AT1R is essential to restore active receptors on the surface of vascular smooth muscle cell, making them available for further stimulation and that caveolae by interfering with internalization limit AT1R availability and thus constrictions. (OTKA T48376, K71591, F48837; ETT 364/2006, and AHA 0855910D, 0735540T, USA)