Exploring AT1 and AT2 angiotensin II receptors in humans

The physiological effects of angiotensin II (Ang II) are mediated through specific AT(1) and AT(2) receptors. Tissue distribution and affinity of these receptors have been explored in binding studies, reverse transcriptase-polymerase chain reaction and in situ hybridisation. Sequencing has also demonstrated gene polymorphisms for both AT(1) and AT(2) receptors. Numerous potent nonpeptide antagonists of angiotensin converting enzyme or of AT receptors have been developed, thus providing a precise analysis of the physiology of the renin-angiotensin system. AT(1) receptors are widely expressed throughout adult tissues, while AT(2) receptors are mainly expressed in the fetus. Receptor density on the cell surface is regulated by multiple hormonal, cytokine and metabolic factors, and is thus profoundly affected by various pathological conditions, especially in the myocardium, kidney and blood vessels. To date, the precise molecular basis for these modifications has not been fully explained, although it may rely in part upon AT receptor gene polymorphisms, which could thus constitute increased risk factors for cardiovascular disease. AT(1) and AT(2) receptor expression is therefore influenced by both age and environmental specifications and is likely to be increased by a diet rich in salt or cholesterol, thus justifying the use of Ang II receptor antagonists in morbidity-mortality studies in high-risk patients.