Modulation and function of extrarenal angiotensin receptors

Historically, physiological modulation of the activity of the renin-angiotension system (RAS) was thought to be mediated only by changes in renin secretion. Hence, altered dietary sodium (Na) intake, changes in renal perfusion pressure, and/or renal adrenoreceptor activity would lead to changes in renin release and plasma angiotensin II (Ang II) concentration, which in turn contribute to regulation of blood pressure and sodium balance. Later, it became apparent that angiotensinogen availability and Ang-converting enzyme activity are also rate-limiting factors that influence the activity of RAS. Finally, over the past few years, evidence has accumulated that indicates the number of Ang II receptors and their subtypes are of great importance in regulating the activity and function of RAS. Cloning of the Ang II receptor genes, development of specific receptor-antagonist ligands, and establishment of genetically mutated animal models have led to greater understanding of the role of Ang II receptors in the regulation of RAS function and activity. This review focuses on the functions and regulation of Ang II receptors in vascular tissues and in the adrenal gland. The authors suggest that identification of control elements for Ang II receptor expression, which are tissue-specific, may provide a basis for future therapeutic manipulation of Ang II receptors in cardiovascular disease states.