Involvement of angiotensin II and endothelin-1 in the development of submandibular gland hypertrophy in response to isoproterenol in rats

We investigated whether angiotensin II (Ang II) and endothelin-1(ET-1) are involved in submandibular hypertrophy in response to repeated treatment with isoproterenol (ISO) in rats. The immunoreactive Ang II (IRAng II) and immunoreactive ET-1 (IRET-1) contents of ISO-induced hypertrophy were significantly higher than those of control glands. Treatment of isolated gland tissues with ISO (1 μM) or dobutamine (1 μM) caused significant increases in the IRAng II and IRET-1 contents of the glands compared with controls. These increases were suppressed by pretreatment with enalapril (3 μM) or captopril (3 μM). Treatment with Ang II (10 μM) also caused an increase in IRET-1 content. Our findings suggest that Ang II and ET-1 are involved in the submandibular gland hypertrophy that develops in rats repeatedly treated with ISO, and that these biologically active peptides may act as growth factors. They also imply that the tissue renin-angiotensin system and Ang II specific receptors are present in the submandibular glands.