In the classical renin-angiotensin system, circulating angiotensin II mediates growth stimulatory and hemodynamic effects through the plasma membrane angiotensin II type I receptor, AT1. Angiotensin II also exists in the intracellular space in some native cells and tissues and can be upregulated in diseases including hypertension and diabetes. Moreover, intracellular AT1 receptors can be found associated with endosomes, nuclei and mitochondria. Intracellular angiotensin II can function in a canonical fashion through the native receptor and also in a non-canonical fashion through interaction with alternative proteins. Likewise the receptor and proteolytic fragments of the receptor can function independent of angiotensin II. Participation of the receptor and ligand in alternative intracellular pathways may serve to amplify events that are initiated at the plasma membrane. We review historical and current literature relevant to angiotensin II, as compared to other intracrines, in tissue culture and transgenic models. In particular, we describe a new transgenic mouse model which demonstrates that intracellular angiotensin II is linked to high blood pressure. Appreciation of the diverse, pleiotropic intracellular effects of components of the renin-angiotensin system should lead to alternative disease treatment targets and new therapies.
- nuclear intracrine
- intracellular angiotensin II
- Copyright © 2011, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology