Mesangial AT sub(1)/B sub(2) Receptor Heterodimers Contribute to Angiotensin II Hyperresponsiveness in Experimental Hypertension

• Published in: Journal of molecular neuroscience Vol. 26; no. 2-3; pp. 185 - 192
• Main Authors: AbdAlla, S, Abdel-Baset, A, Lother, H, el Masslery, A, Quitterer, U
• Format: Journal Article
• Language: English
• Published: 01-06-2005
• ISSN: 0895-8696

Angiotensin II plays a central role in the pathogenesis of hypertension and of related cardiovascular disorders by binding to and activating angiotensin II receptors (AT sub(1) receptors). Sensitization to the vasopressor response of angiotensin II is a key feature in many cardiovascular disorders. However, underlying mechanisms responsible for angiotensin II hypersensitivity are barely understood. Because angiotensin II responsiveness of AT sub(1) receptors can be specifically modified by AT sub(1)/B sub(2) receptor dimerization, we determined the AT sub(1) receptor dimerization status in an experimental model of hypertension. AT sub(1)/B sub(2) receptor heterodimers were abundant on renal mesangial cells isolated from spontaneously hypertensive rats compared with that on cells from normotensive controls. Heterodimerization of AT sub(1) with B sub(2) receptors was correlated with high levels of B sub(2) receptor protein on kidneys and on mesangial cells of hypertensive rats, as determined in immunoblot with receptor-specific antibodies. Specific inhibition of AT sub(1)/B sub(2) receptor heterodimers revealed that these receptor heterodimers mediated an enhanced angiotensin II-stimulated G alpha sub( alpha /11) activation and an increased endothelin-1 secretion of mesangial cells from hypertensive rats. Thus, AT sub(1)/B sub(2) receptor heterodimerization contributes to angiotensin II hyperresponsiveness of mesangial cells in experimental hypertension.